Skip to main content

Advertisement

Log in

Evaluation of the Effects of Fructose on Oxidative Stress and Inflammatory Parameters in Rat Brain

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Hereditary fructose intolerance is an autosomal recessive disorder characterized by the accumulation of fructose in tissues and biological fluids of patients. The disease results from a deficiency of aldolase B, responsible for metabolizing fructose in the liver, kidney, and small intestine. We investigated the effect of acute fructose administration on oxidative stress and neuroinflammatory parameters in the cerebral cortex of 30-day-old Wistar rats. Animals received subcutaneous injection of sodium chloride (0.9 %) (control group) or fructose solution (5 μmol/g) (fructose group). One hour later, the animals were euthanized and the cerebral cortex was isolated. Oxidative stress (levels of thiobarbituric acid-reactive substances (TBA-RS), carbonyl content, nitrate and nitrite levels, 2′,7′-dihydrodichlorofluorescein (DCFH) oxidation, glutathione (GSH) levels, as well as the activities of catalase (CAT) and superoxide dismutase (SOD)) and neuroinflammatory parameters (TNF-α, IL-1β, and IL-6 levels and myeloperoxidase (MPO) activity) were investigated. Acute fructose administration increased levels of TBA-RS and carbonyl content, indicating lipid peroxidation and protein damage. Furthermore, SOD activity increased, whereas CAT activity was decreased. The levels of GSH, nitrate, and nitrite and DCFH oxidation were not altered by acute fructose administration. Finally, cytokines IL-1β, IL-6, and TNF-α levels, as well as MPO activity, were not altered. Our present data indicate that fructose provokes oxidative stress in the cerebral cortex, which induces oxidation of lipids and proteins and changes of CAT and SOD activities. It seems therefore reasonable to propose that antioxidants may serve as an adjuvant therapy to diets or to other pharmacological agents used for these patients, to avoid oxidative damage to the brain.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Scriver CR, Beaudt AL, Sly WL, Valle D (2001) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York

    Google Scholar 

  2. Hommes FA (1993) Inborn errors of fructose metabolism. Am J Clin Nutr 58:788–795

    Google Scholar 

  3. Cox TM (1994) Aldolase B and fructose intolerance. Faseb J 8:62–71

    CAS  PubMed  Google Scholar 

  4. Chambers RA, Pratt RTC (1956) Idiosyncrasy to fructose. Lancet 2:340

    Article  Google Scholar 

  5. Lameire N, Mussche M, Baele G, Kint J, Ringoir S (1978) Hereditary fructose intolerance: a difficult diagnosis in the adult. Am J Med 65:416–423

    Article  CAS  PubMed  Google Scholar 

  6. Morris RC (1968) An experimental renal acidification defect in patients with hereditary fructose intolerance. II. Its distinction from classic renal tubular acidosis; its resemblance to the renal acidification defect associated with the Fanconi syndrome of children with cystinosis. J Clin Invest 47:1648

    Article  PubMed Central  PubMed  Google Scholar 

  7. Odièvre M, Gentil C, Gautier M, Alagille D (1978) Hereditary fructose intolerance in childhood. Diagnosis, management, and course in 55 patients. Am J Dis Child 132:605–608

    Article  PubMed  Google Scholar 

  8. Steinmann B, Gitzelmann R, Van den Berghe G (2001) Disorders of fructose metabolism. In: Scriver CR, Beaudt AL, Sly WL, Valle D (eds) The metabolic and molecular bases of inherited disease, 8th edn. McGraw-Hill, New York

    Google Scholar 

  9. Labrune P, Chatelon S, Huguet P, Odievre M (1990) Unusual cerebral manifestations in hereditary fructose intolerance. Arch Neurol 47:1243–1244

    Article  CAS  PubMed  Google Scholar 

  10. Johnson RJ, Segal MS, Sautin Y, Nakagawa T, Feig DI, Kang DH, Gersch MS, Benner S, Sánchez-Lozada LG (2007) Potential role of sugar (fructose) in the epidemic of hypertension, obesity and the metabolic syndrome, diabetes, kidney disease, and cardiovascular disease. Am J Clin Nutr 86:899–906

    CAS  PubMed  Google Scholar 

  11. Marthaler TM, Froesch ER (1967) Hereditary fructose intolerance. Dental status of eight patients. Br Dent J 123:597

    CAS  PubMed  Google Scholar 

  12. Oberhaensli RD, Rajagopalan B, Taylor DJ, Radda GK, Collins JE, Leonard JV, Schwarz H, Herschkowitz N (1987) Study of hereditary fructose intolerance by use of 31P magnetic resonance spectroscopy. Lancet 2:931–934

    Article  CAS  PubMed  Google Scholar 

  13. Mayatepek E, Hoffmann B, Meissner T (2010) Inborn errors of carbohydrate metabolism. Best Pract Res Clin Gastroenterol 24:607–618

    Article  CAS  PubMed  Google Scholar 

  14. Pagliassotti MJ, Prach PA, Koppenhafer TA, Pan DA (1996) Changes in insulin action, triglycerides, and lipid composition during sucrose feeding in rats. Am J Physiol Regul Integr Comp Physiol 271:1319–1326

    Google Scholar 

  15. Reaven GM (1988) Banting lecture. Role of insulin resistance in human disease. Diabetes 37:1595–1607

    Article  CAS  PubMed  Google Scholar 

  16. Elliott SS, Keim NL, Stern JS, Teff K, Havel PJ (2002) Fructose, weight gain, and the insulin resistance syndrome. Am J Clin Nutr 76:911–922

    CAS  PubMed  Google Scholar 

  17. den Boer M, Voshol PJ, Kuipers F, Havekes LM, Romijn JA (2004) Hepatic steatosis: a mediator of the metabolic syndrome. Lessons from animal models. Arterioscler Thromb Vasc Biol 24:644–649

    Article  Google Scholar 

  18. Rutledge AC, Adeli K (2007) Fructose and the metabolic syndrome: pathophysiology and molecular mechanisms. Nutr Rev 65:13–23

    Article  Google Scholar 

  19. Agrawal R, Pinilla FG (2012) Metabolic syndrome in the brain: deficiency in omega-3 fatty acid exacerbates dysfunctions in insulin receptor signalling and cognition. J Physiol 590:2485–2499

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  20. Klein J, Hurwitz R, Olsen N (1946) Distribution of intravenously injected fructose and glucose between blood and brain. J Biol Chem 164:509–512

    CAS  PubMed  Google Scholar 

  21. Thurston JH, Levy CA, Warren SK, Jones EM (1972) Permeability of the blood–brain barrier to fructose and the anaerobic use of fructose in the brains of young mice. J Neurochem 19:1685–1696

    Article  CAS  PubMed  Google Scholar 

  22. Funari VA, Crandall JE, Tolan DR (2007) Fructose metabolism in the cerebellum. Cerebellum 6:130–140

    Article  CAS  PubMed  Google Scholar 

  23. Cao D, Lu H, Lewis TL, Li L (2007) Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J Biol Chem 282:36275–36282

    Article  CAS  PubMed  Google Scholar 

  24. Stranahan AM, Norman ED, Lee K, Cutler RG, Telljohann R, Egan JM, Mattson MP (2008) Diet-induced insulin resistance impairs hippocampal synaptic plasticity and cognition in middle-aged rats. Hippocampus 18:1085–1088

    Article  PubMed Central  PubMed  Google Scholar 

  25. Ross AP, Bartness TJ, Mielke JG, Parent MB (2009) A high fructose diet impairs spatial memory in male rats. Neurobiol Learn Mem 92:410–416

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Stephan BC, Wells JC, Brayne C, Albanese E, Siervo M (2010) Increased fructose intake as a risk factor for dementia. J Gerontol A Biol Sci Med Sci 65:809–814

    Article  CAS  PubMed  Google Scholar 

  27. Van der Borght K, Köhnke R, Göransson N, Deierborg T, Brundin P, Erlanson-Albertsson C, Lindqvist A (2011) Reduced neurogenesis in the rat hippocampus following high fructose consumption. Regul Pept 167:26–30

    Article  PubMed  Google Scholar 

  28. Rafati A, Anvari E, Noorafshan A (2013) High fructose solution induces neuronal loss in the nucleus of the solitary tract of rats. Folia Neuropathol 51:214–221

    Article  PubMed  Google Scholar 

  29. Busserolles J, Rock E, Gueux E, Mazur A, Grolier P, Rayssiguier Y (2002) Short-term consumption of a high sucrose diet has a pro-oxidant effect in rats. Br J Nutr 87:337–342

    Article  CAS  PubMed  Google Scholar 

  30. Mellor K, Ritchie RH, Meredith G, Woodman OL, Morris MJ, Delbridge LM (2010) High-fructose diet elevates myocardial superoxide generation in mice in the absence of cardiac hypertrophy. Nutrition 26:842–848

    Article  CAS  PubMed  Google Scholar 

  31. Kunde SS, Roede JR, Vos MB, Orr ML, Go YM, Park Y, Ziegler TR, Jones DP (2011) Hepatic oxidative stress in fructose-induced fatty liver is not caused by sulfur amino acid insufficiency. Nutrients 3:987–1002

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Monteiro AA, Biella MS, Bristot SF, Streck EL, Schuck PF, Ferreira GC (2012) Characterization of the biochemical profile in serum of young rats submitted to high concentrations of fructose. Rev Inova Saúde 1:116–129

    Google Scholar 

  33. Esterbauer H, Cheeseman KH (1990) Determination of aldehydic lipid peroxidation products: malonaldehyde and 4-hydroxynonenal. Methods Enzymol 186:407–421

    Article  CAS  PubMed  Google Scholar 

  34. Reznick AZ, Packer L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233:357–363

    Article  CAS  PubMed  Google Scholar 

  35. Miranda KM, Espey MG, Wink DA (2001) A rapid, simple spectrophotometric method for simultaneous detection of nitrate and nitrite. Nitric Oxide 5:62–71

    Article  CAS  PubMed  Google Scholar 

  36. Lebel CP, Ischiropoulos H, Bondy SC (1992) Evaluation of the probe 2′,7′-dichlorofluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5:227–231

    Article  CAS  PubMed  Google Scholar 

  37. Browne RW, Armstrong D (1998) Reduced glutathione and glutathione disulfide. Methods Mol Biol 108:347–352

    CAS  PubMed  Google Scholar 

  38. Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  CAS  PubMed  Google Scholar 

  39. Bannister JV, Calabrese L (1987) Assays for superoxide dismutase. Methods Biochem Anal 32:279–312

    Article  CAS  PubMed  Google Scholar 

  40. Liaudet L, Mabley JG, Soriano FG, Pacher P, Marton A, Haskó G, Szabó C (2001) Inosine reduces systemic inflammation and improves survival in septic shock induced by cecal ligation and puncture. Am J Respir Crit Care Med 164:1213–1220

    Article  CAS  PubMed  Google Scholar 

  41. Coffee EM, Yerkes L, Ewen EP, Zee T, Tolan DR (2009) Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. J Inherit Metab Dis 33:33–42

    Article  PubMed Central  PubMed  Google Scholar 

  42. Fox IH, Kelley WN (1972) Studies on the mechanism of fructose-induced hyperuricemia in man. Metabolism 21:713

    Article  CAS  PubMed  Google Scholar 

  43. Kogut MD, Roe TF, Won NG, Donnell GN (1975) Fructose-induced hyperuricemia observations in normal children and in patients with hereditary fructose intolerance and galactosemia. Pediatr Res 9:774

    Article  CAS  PubMed  Google Scholar 

  44. Vandercammen A, van Schaftingen E (1990) The mechanism by which rat liver glucokinase is inhibited by the regulatory protein. Eur J Biochem 191:483

    Article  CAS  PubMed  Google Scholar 

  45. Yokozawa T, Kim HJ, Cho EJ (2008) Gravinol ameliorates high-fructose-induced metabolic syndrome through regulation of lipid metabolism and proinflammatory state in rat. J Agric Food Chem 56:5026–5032

    Article  CAS  PubMed  Google Scholar 

  46. Chan SM, Sun RQ, Zeng XY, Choong ZH, Wang H, Watt MJ, Ye JM (2013) Activation of PPARα ameliorates hepatic insulin resistance and steatosis in high fructose-fed mice despite increased endoplasmic reticulum stress. Diabetes 62:2095–2105

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  47. Perez-Severiano F, Rios C, Segovia J (2000) Striatal oxidative damage parallels the expression of a neurological phenotype in mice transgenic for the mutation of Huntington’s disease. Brain Res 862:234–237

    Article  CAS  PubMed  Google Scholar 

  48. Mancuso M, Coppede F, Migliore L, Siciliano G, Murri L (2006) Mitochondrial dysfunction, oxidative stress and neurodegeneration. J Alzheimer Dis 10:59–73

    CAS  Google Scholar 

  49. Latini A, Scussiato K, Rosa RB, Leipnitz G, Llesuy S, Bello- Klein A, Dutra-Filho CS, Wajner M (2003) Induction of oxidative stress by L-2-hydroxyglutaric acid in rat brain. J Neurosci Res 74:103–110

    Article  CAS  PubMed  Google Scholar 

  50. Sgaravatti AM, Sgarbi MB, Testa CG, Durigon K, Pederzolli CD, Prestes CG, Wyse AT, Wannmacher CM, Wajner M, Dutra-Filho CS (2007) Gama-hydroxybutyric acid induces oxidative stress in cerebral cortex of young rats. Neurochem Int 50:564–570

    Article  CAS  PubMed  Google Scholar 

  51. Levin B, Oberholzer VG, Snodgrass GJAI, Stimmler L, Wilmers MJ (1963) Fructosaemia, an inborn error of fructose metabolism. Arch Dis Child 38:220–230

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  52. Andreollo NA, dos Santos EF, Araújo MR, Lopes LR (2012) Rat’s age versus human’s age: what is the relationship? Arq Bras Cir Dig 5:49–51

    Article  Google Scholar 

  53. Halliwell B (2011) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18:685–716

    Article  Google Scholar 

  54. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230

    Article  CAS  PubMed  Google Scholar 

  55. Rothe G, Valet G (1990) Flow cytometric analysis of respiratory burst activity in phagocytes with hydroethidine and 2′,7′-dichlorofluorescin. J Leukoc Biol 47:440–448

    CAS  PubMed  Google Scholar 

  56. Huang X, Frenkel K, Klein CB, Costa M (1993) Nickel induces increased oxidants in intact cultured mammalian cells as detected by dichlorofluorescein fluorescence. Toxicol Appl Pharmacol 120:29–36

    Article  CAS  PubMed  Google Scholar 

  57. Halliwell B, Clement MV, Long LH (2000) Hydrogen peroxide in the human body. FEBS Lett 486:10–13

    Article  CAS  PubMed  Google Scholar 

  58. Eraslan G, Saygi S, Essìz D, Aksoy A, Gul H, Macit E (2007) Evaluation of aspect of some oxidative stress parameters using vitamin E, proanthocyanidin and N-acetylcysteine against exposure to cyfluthrin in mice. Pestic Biochem Physiol 88:43–49

    Article  CAS  Google Scholar 

  59. Halliwell B (1991) Reactive oxygen species in living systems: source, biochemistry, and role in human disease. Am J Med 91:14–22

    Article  Google Scholar 

  60. Spruss A, Kanuri G, Wagnerberger S, Haub S, Bischoff SC, Bergheim I (2009) Toll-like receptor 4 is involved in the development of fructose-induced hepatic steatosis in mice. Hepatology 50:1094–1104

    Article  CAS  PubMed  Google Scholar 

  61. Tsai J, Zhang R, Qiu W, Su Q, Naples M, Adeli K (2009) Inflammatory NF-kB activation promotes hepatic apolipoprotein B100 secretion: evidence for a link between hepatic inflammation and lipoprotein production. Am J Physiol Gastrointest Liver Physiol 296:G1287–G1298

    Article  CAS  PubMed  Google Scholar 

  62. Halliwell B, Gutteridge JMC (1996) Oxygen radicals and nervous system. Trends Neurosci 8:22–26

    Article  Google Scholar 

Download references

Acknowledgments

This study was supported by grants from Conselho Nacional de Pesquisa e Desenvolvimento (CNPq), Universidade do Extremo Sul Catarinense (UNESC), and Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC project, PRONEX). We thank Soliany Grassi Maravai for the determination of fructose levels in the serum of the animals.

Conflict of Interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Patrícia Fernanda Schuck.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lopes, A., Vilela, T.C., Taschetto, L. et al. Evaluation of the Effects of Fructose on Oxidative Stress and Inflammatory Parameters in Rat Brain. Mol Neurobiol 50, 1124–1130 (2014). https://doi.org/10.1007/s12035-014-8676-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-014-8676-y

Keywords

Navigation