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Curr Ther Res Clin Exp. 2004 Jan;65(1):79-89. doi: 10.1016/S0011-393X(04)90007-0.

Effects of rosiglitazone treatment on the pentose phosphate pathway and glutathione-dependent enzymes in liver and kidney of rats fed a high-fat diet.

Current therapeutic research, clinical and experimental

Esen Akbay, Nuriye Nuray Ulusu, Füsun Töröner, Göksun Ayvaz, Ferit Taneri, Müjde Aktürk, Metin Arslan, Cimen Karasu

Affiliations

  1. Department of Endocrinology, Faculty of Medicine, Mersin University, Mersin, Turkey.
  2. Department of Biochemistry, Faculty of Medicine, Hacettepe University, Ankara, Turkey.
  3. Departments of Endocrinology-Metabolism, Gazi University, Ankara, Turkey.
  4. Department of Surgery, Gazi University, Ankara, Turkey.
  5. Department of Medical Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.

PMID: 24936106 PMCID: PMC4052959 DOI: 10.1016/S0011-393X(04)90007-0

Abstract

BACKGROUND: Animals fed high-fat diets have been shown to develop hyperglycemia, insulin resistance, hyperlipidemia, and moderate obesity, which resemble the human metabolic syndrome. Obesity, the metabolic syndrome, and some thiazolidinediones, which act as insulin sensitizers, may increase oxidative stress, and/or influence the levels of cellular reducing equivalents and homeostasis.

OBJECTIVE: This study investigated the effects of a high-fat diet, rosiglitazone, or a high-fat diet plus rosiglitazone on metabolic syndrome parameters and crucial liver and kidney enzyme activities in rats.

METHODS: Male Wistar rats were assigned to 4 groups (n = 6 per group): (1) the fat (F) group was fed a rodent diet comprising 45 kcal% fat, (2) the rosiglitazone (R) group was fed a standard rat chow comprising 4.97 kcal% fat plus rosiglitazone (3 mg/kg.d), (3) the fat + rosiglitazone (FR) group was fed a rodent diet comprising 45 kcal% fat (as lard, product D12451) plus rosiglitazone (3 mg/kg.d), and (4) the control (C) group was fed a standard rat chow comprising 4.97 kcal% fat. Animals were housed for 4 weeks, at which time the liver and kidney were isolated for spectrophotometric determination of enzyme activities. Body weight was measured before treatment (baseline) and then weekly throughout the study. Adiposity was measured at the end of the 4 weeks.

RESULTS: The activities of glucose-6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6-PGD), glutathione reductase (GR), and glutathione-S-transferase (GST) were significantly reduced in the livers of groups F, R, and FR compared with group C (all P < 0.05). Kidney G6PD, 6-PGD, and GR were found to be significantly lower in group R compared with the other groups (all P < 0.05). Kidney GST was similar in all groups. Plasma glucose, triglyceride, and insulin concentrations were significantly higher than in group F versus the other groups (all P < 0.05). Adiposity was increased in groups F and FR compared with groups C and R (all P < 0.05). Serum cholesterol concentrations were similar in all groups.

CONCLUSIONS: In this study, high-fat diet in rats decreased the enzyme activities responsible for pentose phosphate pathway and glutathione-dependent metabolism in liver but not in kidney. Similarly, these enzyme activities were inhibited with rosiglitazone treatment alone in both organs.

Keywords: glutathione-dependent metabolism; high-fat diet; metabolic syndrome; obesity; pentose phosphate pathway; rat; rosiglitazone

References

  1. Drug Metab Dispos. 1999 Jun;27(6):695-700 - PubMed
  2. Lipids. 1993 Jul;28(7):657-62 - PubMed
  3. J Biol Chem. 2002 Aug 16;277(33):29681-5 - PubMed
  4. Anal Biochem. 1976 May 7;72:248-54 - PubMed
  5. Annu Rev Biochem. 2001;70:341-67 - PubMed
  6. J Nutr Biochem. 2003 Jan;14(1):17-23 - PubMed
  7. Cell Biochem Funct. 1986 Oct;4(4):241-7 - PubMed
  8. Mol Cell Biochem. 1991 Jun 26;105(1):1-5 - PubMed
  9. Am J Epidemiol. 2001 Aug 15;154(4):348-56 - PubMed
  10. Am J Physiol. 1989 Oct;257(4 Pt 1):L163-73 - PubMed
  11. Clin Ther. 2000 Oct;22(10):1151-68; discussion 1149-50 - PubMed
  12. Br J Pharmacol. 1999 Dec;128(7):1570-6 - PubMed
  13. Diabetes. 1996 Dec;45(12):1661-9 - PubMed
  14. J Nutr. 1978 Jun;108(6):981-7 - PubMed
  15. Hum Exp Toxicol. 1994 Nov;13 Suppl 2:S1-117 - PubMed
  16. Biochem Cell Biol. 1990 Jul-Aug;68(7-8):989-98 - PubMed
  17. J Biol Chem. 2003 Jan 3;278(1):263-9 - PubMed
  18. J Nutr Sci Vitaminol (Tokyo). 1998 Feb;44(1):89-102 - PubMed
  19. Chem Biol Interact. 2002 Nov 10;142(1-2):57-71 - PubMed
  20. Int J Biochem Cell Biol. 1999 Jul;31(7):787-96 - PubMed
  21. FEBS Lett. 1989 Jun 19;250(1):72-4 - PubMed
  22. J Biochem Mol Toxicol. 2001;15(2):107-13 - PubMed
  23. Free Radic Res. 1999 Oct;31(4):273-300 - PubMed
  24. Proc Soc Exp Biol Med. 1994 Feb;205(2):186-9 - PubMed
  25. Cytometry A. 2003 Mar;52(1):28-35 - PubMed
  26. Int J Obes Relat Metab Disord. 1994 Jan;18(1):25-33 - PubMed
  27. Toxicol Sci. 2001 Apr;60(2):271-8 - PubMed
  28. Ann N Y Acad Sci. 1982;386:81-110 - PubMed
  29. Biochem Pharmacol. 1992 Apr 15;43(8):1868-71 - PubMed
  30. Methods Enzymol. 1975;41:220-6 - PubMed
  31. J Biol Chem. 1974 Nov 25;249(22):7130-9 - PubMed
  32. Chem Res Toxicol. 2001 Aug;14(8):965-74 - PubMed
  33. Annu Rev Nutr. 1985;5:365-90 - PubMed

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