Effect of Prolonged High-Fat Diet on Thiol-Disulfide Homeostasis in Rats

Yulia K. Denisenko, PhD, ScD*; Tatyana P. Novgorodtseva, PhD

Vladivostok Affiliation of Far-Eastern Research Centre for Physiology and Respiratory Pathology of SB RAMS – Institute of Medical Climatology and Rehabilitative Treatment, Vladivostok, Russian Federation

*Corresponding author: Yulia K. Denisenko, Ph.D, ScDi. Head of Laboratory of biomedicine researches. Vladivostok Affiliation of Far-Eastern Research Centre for Physiology and Respiratory Pathology of SB RAMS – Institute of Medical Climatology and Rehabilitative Treatment. Vladivostok, Russian Federation. E-mail: karaman@inbox.ru

Published: September 24, 2013


The aim of this study was to determine the effect of a prolonged high-fat (HF) on thiol-disulfide homeostasis via the activity of the glutathione redox-system (GRS) in rat blood and liver.

Methods: The experiment was conducted on male Wistar rats. They were divided into groups and fed on the HF diet for 30, 90 and 180 days, respectively. The HF diet consisted of beef fat and cholesterol (19 % and 2 % of the total diet, respectively). The state of the GRS was assessed in the erythrocytes and liver tissue by the glutathione, glutathione reductase (GR) and glutathione peroxidase (GP) activity. The levels of the initial and final products of lipid peroxidation – lipid hydroperoxides (LOOHs), diene conjugates (DC) and malondialdehydes (MDA) in the blood and liver were investigated.

Results: Within 30 days, the HF diet inhibits the glutathione enzyme activity in the blood (GR: P<0.01; GP: P<0.001) and liver (GR, P<0.01). Within 90 days the HF diet kick-starts the beginning of the GRS compensatory response and restores the thiol-disulfide homeostasis. At 180 days, the HF diet shows failure of the compensatory processes in the glutathione system caused by the redox-imbalance in the thiol-disulfide exchange, which reveals lowered levels of glutathione, GR and GP activity (P<0.001 for all) in the blood and liver.

Conclusion: Our results suggest that the thiol-disulfide status of the cells depends upon the nature of the nutrition, a long-term breach of which triggers a compensatory response and a failure of the compensatory processes in the GRS.

  1. Zhang Y, Du Y, Le W, Wang K, Kieffer N, Zhang J. Redox Control of the survival of healthy and diseased cells. Antioxid Redox Signal 2011; 15(11):2867-908.
  2. Iton K, Ishii T, Wakabayashi N, Yamomoto M. Regulatory mechanisms of cellular response to oxidative stress. Free Radic Res 1999; 31(4):319-24.
  3. Poole LB, Karplus PA, Claiborne A.  Protein sulfenic asids in redox signaling. Annu Rev. Pharmacol Toxicol 2004; 44:325-47.
  4. Filomeni G, Rotilio G, Ciriolo MR. Cell signalling and the glutathione redox system. Biochem Pharmacol 2002, 64(5-6):1057-64.
  5. Schafer FQ, Beuttner GR. Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med 2001; 30(11):1191–212.
  6. Forman HJ, Fukuto JM, Torres M. Redox signaling: thiol chemistry defines which reactive oxygen and nitrogen species can act second messengers. Am J Physiol Cell Physiol 2004; 287(2):246-56.
  7. Sen CK. Cellular thiols and redox-regulated signal transduction. Curr Top Cell Regul 2000; 36:1-30.
  8. Meister A, Anderson ME. Glutathione. Ann Rev Biochem 1983; 52:711-60.
  9. Sies H. Glutathione and its role in cellular functions. Free Radic Biol Med 1999; 27(9-10):916-21.
  10. Pastore A, Piemonte F. S-Glutathionylation signaling in cell biology: progress and prospects. Eur J Pharm Sci 2012; 46(5):279-92.
  11. Kulinskii VI, Kolesnichenko LS. Glutathione system. I. Synthesis, transport, glutathione transferases, glutathione peroxidases. Biomed Khim 2009; 55(3):255-77. [Article in Russian].
  12. Kulinskii VI, Kolesnichenko LS. Glutathione system. II. Other enzymes, thiol-disulfide metabolism, inflammation and immunity, functions. Biomed Khim 2009; 55(4):365-79. [Article in Russian].
  13. Brigelius-Flohe R. Tissue-specific functions of individual glutathione peroxidases. Free Radic Biol Med 1999; 27(9-10):951-65.
  14. Siems WG, Sommerburg O, Grune T. Erythrocyte free radical and energy metabolism. Clin Nephrol 2000; 53(1 Suppl):S9-17.
  15. Lu SC. Regulation of hepatic glutathione synthesis: current concepts and controversies. FASEB 1999; 13(10):1169-83.
  16. Novgorodtseva TP, Karaman YuK, Zhukova NV. The effect of high fat food on erythrocyte phospholipids, fatty acids composition and glutathione redox-system of rats with alimentary dyslipidemia. The Health 2010; 2(1):45-50.
  17. Karaman YuK, Novgorodtseva TP, Zhukova NV. Phospholipid composition of erythrocytes and glutathione redox system in rats during adaptation to cholesterol load. Bull Exp Biol Med 2011; 150(3):291-94.
  18. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes. Strasburg, 18.III.1986. http://conventions.coe.int/ treaty/en/treaties/html/123.htm.
  19. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys 1959; 82(1):70-7.
  20. Ramos-Martines IL, Torres AM. Glutathione reductase of mantle tissue from sea mussel medulis. 1. Рurification and characterization two seasonal enzymatic forms. Biochem Physiol 1985; 80(213): 355-360.
  21. Mills GC. The purification and properties of glutathione peroxidase of erythrocytes. J Biol Chem 1959; 234(3):502-6.
  22. Yagi K. Lipid peroxides and human diseases. Chem Phys Lipids 1987; 45(2-4):337-51.
  23.  Dalton TP, Shertzer HG, Puga A. Regulation of gene expression by reactive oxygen. Annu Rev Pharmacol Toxicol 1999; 39:67-101.
  24. McIntyre TM, Zimmerman GA, Prescott SM. Biologically active oxidized phospholipids. J Biol Chem 1999; 274(36):25189-92.
  25. Novo E, Parola M. Redox mechanisms in hepatic chronic wound healing and fibrogenesis. Fibrogenesis Tissue Repair 2008; 1(1):5.

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Int J Biomed. 2013; 3(3):197-200. © 2013 International Medical Research and Development Corporation. All rights reserved.