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N-3 Fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring

Abstract

Objective:

We investigated the role of dietary n-3 polyunsaturated fatty acids (n-3 PUFA) in the modulation of total antioxidant status in streptozotocin (STZ)-induced diabetic rats and their macrosomic offspring.

Design:

Female wistar rats, fed on control diet or n-3 PUFA diet, were rendered diabetic by administration of five mild doses of STZ on day 5 and were killed on days 12 and 21 of gestation. The macrosomic (MAC) pups were killed at the age of 60 and 90 days.

Measurements:

Lipid peroxidation was measured as the concentrations of plasma thiobarbituric acid reactive substances (TBARS), and the total antioxidant status was determined by measuring (i) plasma oxygen radical absorbance capacity (ORAC), (ii) plasma vitamin A, E and C concentrations, and (iii) antioxidant enzymes activities in erythrocytes. The plasma lipid concentrations and fatty acid composition were also determined.

Results:

Diabetes increased plasma triglyceride and cholesterol concentrations, whereas macrosomia was associated with enhanced plasma cholesterol and triglyceride levels, which diminished by feeding n-3 PUFA diet. N-3 PUFA diet also reduced increased plasma TBARS and corrected the decreased ORAC values in diabetic rats and their macrosomic offspring. EPAX diet increased the diminished vitamin A levels in diabetic mothers and vitamin C concentrations in macrosomic pups. Also, this diet improved the decreased erythrocyte superoxide dismutase and glutathione peroxidase activities in diabetic and macrosomic animals.

Conclusion:

Diabetes and macrosomia were associated with altered lipid metabolism, antioxidant enzyme activities and vitamin concentrations. N-3 PUFA diet improved hyperlipidemia and restored antioxidant status in diabetic dams and MAC offspring.

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References

  1. Kannel WB, McGee DL . Diabetes and cardiovascular disease: the Framingham Study. JAMA 1978; 241: 2035–2038.

    Article  Google Scholar 

  2. Baynes JW, Thorpe SR . Role of oxidative stress in diabetic complications. Diabetes 1999; 48: 581–589.

    Article  Google Scholar 

  3. Kamath U, Rao G, Raghothama C, Rai L, Rao P . Erythrocyte indicators of oxidative stress in gestational diabetes. Acta Paediatr 1998; 87: 676–679.

    Article  CAS  PubMed  Google Scholar 

  4. Biesalski HK . The role of antioxidants in nutritional support. Nutrition 2000; 16: 578–581.

    Article  Google Scholar 

  5. Hunt JV, Smith CCT, Wolf SP . Autoxidative glycosylation and possible involvement of peroxides and free radicals in LDL modification by glucose. Diabetes 1990; 39: 1420–1424.

    Article  CAS  PubMed  Google Scholar 

  6. Dincer Y, Alademir Z, Ilkova H, Akcay T . Susceptibility of glutatione and glutathione-related antioxidant activity to hydrogen peroxide in patients with type 2 diabetes: effect of glycemic control. Clin Biochem 2002; 35: 297–301.

    Article  CAS  PubMed  Google Scholar 

  7. McLennan SV, Heffernan S, Wright L, Rae C, Fisher E, Yue DK et al. Changes in hepatic glutathione metabolism in diabetes. Diabetes 1991; 40: 344–348.

    Article  CAS  Google Scholar 

  8. Young IS, Torney JJ, Trimble ER . The effects of ascorbate supplementation on oxidative stress in the streptozotocin diabetic rat. Free Rad Biol Med 1992; 8: 752–758.

    Google Scholar 

  9. Ylonen K, Alfthan G, Groop L, Saloranta C, Aro A, Virtanen SM . Dietary intakes and plasma concentrations of carotenoids and tocopherols in relation to glucose metabolism in subjects at high risk of type 2 diabetes: the Botnia Dietary Study. Am J Clin Nutr 2003; 77: 1434–1441.

    Article  PubMed  Google Scholar 

  10. Elejalde Guerra JL . Oxidative stress, diseases and antioxidant treatment. Ann Med Intern 2001; 18: 326–335.

    CAS  Google Scholar 

  11. Wander RC, Shi-Hua Du . Oxidation of plasma proteins is not increased after supplementation with eicosapentaenoic and docosahexaenoic acids. Am J Clin Nutr 2000; 72: 731–737.

    Article  CAS  PubMed  Google Scholar 

  12. Allard JP, Kurian R, Aghdassi E, Muggli R, Royall D . Lipid peroxidation during n-3 fatty acid and vitamin E supplementation in humans. Lipids 1997; 32: 535–541.

    Article  CAS  PubMed  Google Scholar 

  13. Nordoy A, Bonaa KH, Nilsen H, Berge RK, Hansen JB, Ingerbresten OC . Effects of Simvastatin and omega-3 fatty acids on plasma lipoproteins and lipid peroxidation in patients with combined hyperlipidaemia. J Intern Med 1998; 243: 163–170.

    Article  CAS  PubMed  Google Scholar 

  14. Ando K, Nagata K, Beppu M, Kikugawa K, Kawabata T, Hasegawa K et al. Effect of n-3 fatty acid supplementation on lipid peroxidation and protein aggregation in rat erythrocyte membranes. Lipids 1998; 33: 505–512.

    Article  CAS  PubMed  Google Scholar 

  15. Hunkar T, Aktan F, Ceylan A, Karasu C . Antioxidants in Diabetes-Induced Complications (ADIC) Study Group. Effects of cod liver oil on tissue antioxidant pathways in normal and streptozotocin-diabetic rats. Cell Biochem Funct 2002; 20: 297–302.

    Article  CAS  PubMed  Google Scholar 

  16. Merzouk H, Khan NA . Implication of lipids in macrosomia of diabetic pregnancy: can n-3 polyunsaturated fatty acids exert beneficial effects? Clin Sci 2003; 105: 519–529.

    Article  CAS  PubMed  Google Scholar 

  17. Triboulot C, Hichami A, Denys A, Khan NA . ω-3 dietary polyunsaturated fatty acids diminish hypertension: implication of T-cell signaling mechanisms. J Nutr 2001; 131: 2364–2369.

    Article  CAS  PubMed  Google Scholar 

  18. Guermouche B, Yessoufou A, Soulaimann N, Merzouk H, Moutairou K, Hichami A et al. (N-3) Fatty acids modulate T-cell calcium signaling in obese macrosomic rats. Obes Res 2004; 12: 1744–1753.

    Article  CAS  PubMed  Google Scholar 

  19. Soulaimann-Mokhtari NA, Guermouche B, Yessoufou A, Saker M, Moutairou K, Hichami A et al. Modulation of lipid metabolism by (N-3) PUFA in gestational diabetic rats and their obese offspring. Clin Sci 2005; 109: 287–295.

    Article  Google Scholar 

  20. Calder PC . Dietary fatty acids and the immune system. Lipids 1999; 34: S137–S140.

    Article  CAS  PubMed  Google Scholar 

  21. McLennan PL, Raederstorff D . Diabetes puts myocard n-3 fatty acid status at risk in the absence of supplementation in the rat. Lipids 1999; 34: S91–S92.

    Article  CAS  PubMed  Google Scholar 

  22. Merzouk H, Madani S, Hichami A, Prost J, Belleville J, Khan NA . Age-related changes in faty acids in obese offspring of streptozotocin-induced diabetic rats. Obes Res 2002; 10: 703–714.

    Article  CAS  PubMed  Google Scholar 

  23. Bligh EG, Dyer WJ . A rapid method of total lipid extraction and purification. Can J Biochem Physiol 1995; 37: 911–917.

    Article  Google Scholar 

  24. Merzouk H, Madani S, Hichami A, Prost J, Moutairou K, Belleville J et al. Impaired lipoprotein metabolism in obese offspring of streptozotocin-induced diabetic rats. Lipids 2002; 37: 773–781.

    Article  CAS  PubMed  Google Scholar 

  25. Quintanilha AT, Packer L, Szyszlo DJM, Racanelly TL, Davies KJA . Membrane effects of vitamin E deficiency bioenergetic and surface charge density studies of skeletal muscle and liver mitochondria. Ann NY Acad Sci 1982; 393: 32–47.

    Article  CAS  PubMed  Google Scholar 

  26. Cao G, Alessio HM, Cutler RG . Oxygen-radical absorbance capacity assay for antioxidants. Free Rad Biol Med 1993; 14: 303–311.

    Article  CAS  PubMed  Google Scholar 

  27. Courderot-Masuyer C, Lahet JJ, Verges B, Brun JM, Rochette L . Ascorbyl free radical release in diabetic patients. Cell Mol Biol 2000; 46: 1397–1401.

    CAS  PubMed  Google Scholar 

  28. Roe JH, Kuether CA . The determination of ascorbic acid in whole blood and urine through the 2,4-dinitrophenylhydrazine derivatives of dehydroascorbic acid. J Biol Chem 1943; 147: 399–407.

    CAS  Google Scholar 

  29. Zaman Z, Fielden P, Frost PG . Simultaneous determination of vitamins A and E and carotenoids in plasma by reversed-phase HPLC in elderly and younger subjects. Clin Chem (Washington DC) 1993; 39: 2229–2234.

    CAS  Google Scholar 

  30. Paglia DE, Valentine WN . Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 1967; 70: 158–169.

    CAS  Google Scholar 

  31. Goldberg DM, Spooner RJ . Glutathione reductase. In: Bergmeyer HB (ed). Methods of Enzymatic Analysis, vol. 3. Verlag Chemie: Weinheim, Germany, 1992, pp 258–265.

    Google Scholar 

  32. Elstner EF, Youngman RJ, Obwald W . Superoxide dismutase. In: Bergmeyer HB (ed). Methods of Enzymatic Analysis, vol. 3. Verlag Chemie: Weinheim, Germany, 1983, pp 293–302.

    Google Scholar 

  33. Wood SC, Rao TD, Frey AB . Multidose streptozotocin induction of diabetes in BALB/cBy mice induces a T cell proliferation defect in thymocytes which is reversible by interleukin-4. Cell Immunol 1999; 192: 1–12.

    Article  CAS  PubMed  Google Scholar 

  34. Müller A, Schott-Ohly P, Dohle C, Gleichmann H . Differential regulation of Th1-type and Th2-type cytokine profiles in pancreatic islets of C57BL/6 and BALB/c mice by multiple low doses of streptozotocin. Immunobiol 2002; 205: 35–50.

    Article  Google Scholar 

  35. Herold C, Elhabazi A, Bismuth G, Bensussan A, Boumsell L . CD100 is associated with CD45 at the surface of human T lymphocytes. Role in T cell homotypic adhesion. J Immunol 1996; 157: 5262–5268.

    CAS  PubMed  Google Scholar 

  36. Maksimovic-Ivanic D, Trajkovic V, Miljkovic DJ, Mostarica Stojkovic M, Stosic-Grujicic S . Down-regulation of multiple low dose streptozotocin-induced diabetes by mycophenolate mofetil. Clin Exp Immunol 2002; 129: 214–223.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Elder ME, Maclaren NK . Identification of profound peripheral T lymphocyte immunodeficiencies in the spontaneously diabetic BB rat. J Immunol 1983; 130: 1723–1731.

    CAS  PubMed  Google Scholar 

  38. Serreze DV, Gaskins HR, Leiter EH . Defects in the differentiation and function of antigen presenting cells in NOD/Lt mice. J Immunol 1993; 150: 2534–2543.

    CAS  PubMed  Google Scholar 

  39. Merzouk H, Mandani S, Boualga A, Prost J, Bouchenak M, Belleville J . Age-related changes in cholesterol metabolismin macrosomic offspring of rats with streptozotocin-induced diabetes. J Lipids Res 2001; 42: 1152–1159.

    CAS  Google Scholar 

  40. Buggage RR, Matteson DM, Shen de F, Sun B, Tuaillon N, Chan CC . Effect of sex hormones on experimental autoimmune uveoretinitis (EAU). Immunol Invest 2003; 32: 259–273.

    Article  CAS  PubMed  Google Scholar 

  41. Klein SL, Bird BH, Glass GE . Sex differences in immune responses and viral shedding following Seoul virus infection in Norway rats. Am J Trop Med Hyg 2001; 65: 57–63.

    Article  CAS  PubMed  Google Scholar 

  42. Knopp RH, Warth MR, Charles D, Childs M, Li JR, Mabuchi H et al. Lipoprotein metabolism in pregnancy, fat transport to the fetus, and the effects of diabetes. Biol Neonate 1986; 50: 297–317.

    Article  CAS  PubMed  Google Scholar 

  43. Shafrir E, Khassis S . Maternal–fetal fat transport versus new fat synthesis in the pregnant diabetic rat. Diabetologia 1982; 22: 111–117.

    Article  CAS  PubMed  Google Scholar 

  44. Parini P, Angelin B, Rudling M . Cholesterol and lipoprotein metabolism in aging: reversal of hypercholesterolemia by growth hormone treatment in old rats. Arterioscler Thromb Vasc Biol 1999; 19: 832–839.

    Article  CAS  PubMed  Google Scholar 

  45. Choi YS, Sugano M, Ide T . Sex-difference in the age related change of cholesterol metabolism in rats. Mech Ageing Dev 1988; 44: 91–99.

    Article  CAS  PubMed  Google Scholar 

  46. Merzouk H, Bouchenak M, Loukidi B, Madani S, Prost J, Belleville J . Fetal macrosomia related to maternal poorly controlled type 1 diabetes strongly impairs serum lipoprotein concentrations and composition. J Clin Pathol 2000; 53: 917–923.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Sirtori CR, Galli C . N-3 fatty acids and diabetes. Biomed Pharmacother 2002; 56: 397–406.

    Article  CAS  PubMed  Google Scholar 

  48. Vericel E, Calzada C, Chapuy P, Lagarde M . The influence of low intake of n-3 fatty acids on platelets in elderly people. Atherosclerosis 1999; 147: 187–192.

    Article  CAS  PubMed  Google Scholar 

  49. Mori TA, Dunstan DW, Burke V, Croft KD, Rivera JH, Beilin LJ et al. Effect of dietary fish and exercise training on urinary F2-isoprostrane excretion in non-insulin dependent diabetic patients. Metabolism 1999; 48: 1402–1408.

    Article  CAS  PubMed  Google Scholar 

  50. Yilmaz O, Ozkan Y, Yildirim M, Ozturk AI, Ersan Y . Effects of alpha lipoic acid, ascorbic acid-6-palmitate, and fish oil on glutathione, malonaldehyde and fatty acid levels in erythrocytes of streptozotocine induced diabetic male rats. J Cell Biochem 2002; 86: 530–539.

    Article  CAS  PubMed  Google Scholar 

  51. Kesavulu MM, Kameswararao B, Apparao Ch, Kumar EG, Harinarayan CV . Effect of omega-3 fatty acids on lipid peroxidation and antioxidant enzyme status in type 2 diabetic patients. Diabetes Metab 2002; 28: 20–26.

    CAS  PubMed  Google Scholar 

  52. Sarsilmaz M, Songur A, Ozyurt H, Kus I, Ozen OA, Ozyurt B et al. Potential role of dietary omega-3 essential fatty acids on some oxidant/antioxidant parameters in rats' corpus striatum. Prostaglandins Leukot Essent Fatty Acids 2003; 69: 253–259.

    Article  CAS  PubMed  Google Scholar 

  53. Grundt H, Nilsen DW, Mansoor MA, Nordoy A . Increased lipid peroxidation during long-term intervention with high doses of n-3 fatty acids (PUFAs) following an acute myocardial infraction. Eur J Clin Nutr 2003; 57: 793–800.

    Article  CAS  PubMed  Google Scholar 

  54. Cho SH, Coi YS . Lipid peroxidation and antioxidant status is affected by different vitamin E levels when feeding fish oil. Lipids 1994; 29: 47–52.

    Article  CAS  PubMed  Google Scholar 

  55. Hansen JB, Berge RK, Nordoy A, Bonaa KH . Lipid peroxidation of isolated chylomicrons and oxidative status in plasma after intake of highly purified eicosapentaenoic or docosahexaenoic acids. Lipids 1998; 11: 1123–1129.

    Article  Google Scholar 

  56. Serhan CN, Arita M, Hong S, Gotlinge K . Resolvins, docosatrienes and neuroprotectins, novel omega-3-derived mediators and their endogenous aspirin-tiggered epimers. Lipids 2004; 39: 1125–1132.

    Article  CAS  PubMed  Google Scholar 

  57. Khan NA, Hichami A . Role of N-3 polyunsaturated fatty acids in the modulation of T-cell signalling. In: Pandalai G (ed). Recent Research Developments in Lipids, vol. 6. Transworld Research Network: Trivandrum, Kerala, India, 2002, pp 65–78.

    Google Scholar 

  58. Das UN, Mohan IK, Raju TR . Effect of corticosteroids and eicosapentaenoic acid/docosahexaenoic acid on pro-oxidant and anti-oxidant status and metabolism of essential fatty acids in patients with glomerular disorders. Prostaglandins Leukot Essent Fatty Acids 2001; 65: 197–203.

    Article  CAS  PubMed  Google Scholar 

  59. Yazu K, Yamamoto Y, Niki E, Miki K, Ukegawa K . Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous micelles. II. Effect of antioxidants. Lipids 1998; 33: 597–600.

    Article  CAS  PubMed  Google Scholar 

  60. Herrera E, Ortega H, Alvino G, Giovannini N, Amusquivar E, Cetin I . Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy. Eur J Clin Nutr 2004; 58: 1231–1238.

    Article  CAS  PubMed  Google Scholar 

  61. Dunstan JA, Mori TA, Barden A, Beilin LJ, Holt PG, Calder PC et al. Effects of n-3 polyunsaturated fatty acid supplementation in pregnancy on maternal and foetal erythrocyte fatty acid composition. Eur J Clin Nutr 2004; 58: 429–437.

    Article  CAS  PubMed  Google Scholar 

  62. Herrera E . Implications of dietary fatty acids during pregnancy on placental, foetal and postnatal development – a review. Placenta 2002; 23: S9–S19.

    Article  PubMed  Google Scholar 

  63. Ghebremeskel K, Bistanis D, Koukkou E, Lowry C, Poston L, Crawford MA . Liver triacylglycerols and free fatty acids in streptozotocin-induced diabetic rats have atypical n-6 and n-3 pattern. Com Biochem Physiol Part C 2002; 132: 349–354.

    CAS  Google Scholar 

  64. Dixon G, Nolan J, McClenaghan NH, Flatt PR, Newsholme P . Arachidonic acid palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity. Clin Sci 2004; 106: 191–199.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Office of Scholarship Programme of IDB which granted a scholarship to A. Yessoufou. We also thank the French Embassy at Cotonou, Benin and the French Foreign Office (CMEP), Burgundy Region which sanctioned the contingent grants for this work.

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Yessoufou, A., Soulaimann, N., Merzouk, S. et al. N-3 Fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring. Int J Obes 30, 739–750 (2006). https://doi.org/10.1038/sj.ijo.0803211

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  • DOI: https://doi.org/10.1038/sj.ijo.0803211

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