Oral Supplementation Effect of Iron and its Complex Form With Quercetin on Oxidant Status and on Redistribution of Essential Metals in Organs of Streptozotocin Diabetic Rats

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Abstract

Background and aims: Quercetin, is a polyphenolic antioxidant compound. It is able to form complex with metal ions such as iron and exerts a broad range of biological activities like improving metabolic disorders. This research aims at investigating the effect of oral supplementation of iron (2.5mg Fe/Kg/day) and its complex form (molar ratio 1:5; 2.5mg/25mg/Kg/day) with quercetin (25mg/Kg/day) on lipid metabolism, oxidant status and trace elements contents in organs of Wistar diabetic rats (45 mg/kg/rat.ip of streptozotocin) during eight weeks of experimentation.

Material and method: To achieve this, liver and adipose tissue enzymes activities, NO, O2−•, TBARs, carbonyl protein levels in plasma were analysed. Metals (Cu, Fe, Mg, Zn) analysis of organs were determined by inductively coupled plasma atomic emission spectroscopy.

Results: Iron supplemented alone induced a noticeable disorder in lipid, lipoprotein, lipases and oxidant status. Yet, it caused an imbalance in the redistribution of metals in the organs of diabetic and non diabetic rats. Iron-quercetin complex was shown as less harmful and more beneficial than iron supplemented alone.

Conclusions: This complex could reverse oxidative stress and iron deficiency mostly caused by the diabetic disease but at the same time it induces an imbalance in redistribution of other essential metals.

1. Cho N, Shaw J, Karuranga S et al. IDF Diabetes Atlas: global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract 138: 271-281, 2018.

2. Roghani M, Baluchnejadmojarad T. Hypoglycemic and hypolipidemic effect and antioxidant activity of chronic epigallocatechin-gallate in streptozotocin-diabetic rats. Pathophysiology 17: 55-59, 2010.

3. Presley TD, A’ja VD, Jeffers AB et al. The variation of macro-and micro-minerals of tissues in diabetic and non-diabetic rats. J Trace Elem Med Biol 39: 108-115, 2017.

4. Kimura M, Yokoi K. Iron accumulation in tissues of magnesium-deficient rats with dietary iron overload. Biol Trace Elem Res 51: 177-197, 1996.

5. Viktorinova A, Tošerová E, Križko M et al. Altered metabolism of copper, zinc, and magnesium is associated with increased levels of glycated hemoglobin in patients with diabetes mellitus. Metabolism 58: 1477-1482, 2009.

6. Bansal P, Paul P, Mudgal J et al. Antidiabetic, antihyperlipidemic and antioxidant effects of the flavonoid rich fraction of Pilea microphylla (L.) in high fat diet/streptozotocin-induced diabetes in mice. Exp Toxicol Pathol 64: 651-658, 2012.

7. Najera MO, Tinajero IS, Paez LIR et al. Quercetin improves antioxidant response in diabetes through maintenance of reduced glutathione levels in blood. Afr J Pharm Pharmacol 7: 2531-2539, 2013.

8. Liu Q, Sun L, Tan Y et al. Role of iron deficiency and overload in the pathogenesis of diabetes and diabetic complications. Curr Med Chem 16: 113-129, 2009.

9. van Acker SA, van Balen GP, van den Berg DJ et al. Influence of iron chelation on the antioxidant activity of flavonoids. Biochem Pharmacol 56: 935-943, 1998.

10. Berroukeche F, Mokhtari-Soulimane N, Imessaoudene A et al. Iron-quercetin complex reduces lipid and protein oxidation in streptozotocin diabetic rats complications independently to glucose lowering. WJPR 5: 1690-1723, 2016.

11. Burstein M, Fine A, Atger Vr et al. Rapid method for the isolation of two purified subfractions of high density lipoproteins by differential dextran sulfate-magnesium chloride precipitation. Biochimie 71: 741-746, 1989.

12. Bouanane S, Merzouk H, Benkalfat NB et al. Hepatic and very low-density lipoprotein fatty acids in obese offspring of overfed dams. Metabolism 59: 1701-1709, 2010.

13. Levine RL, Garland D, Oliver CN et al. Determination of carbonyl content in oxidatively modified proteins. Methods Enzymol 1990: 464-478

14. Draper H, Hadley M. Malondialdehyde determination as index of lipid Peroxidation. Methods Enzymol 1990: 421-431

15. Anderson M, Greenwald Re. Handbook of methods for oxygen radical research. Florida: CRC Press Inc: 317-323, 1985.

16. Guevara I, Iwanejko J, Dembińska-Kieć A et al. Determination of nitrite/nitrate in human biological material by the simple Griess reaction. Clin Chim Acta 274: 177-188, 1998.

17. Chvapil M, Peng YM, Aronson AL et al. Effect of zinc on lipid peroxidation and metal content in some tissues of rats. J Nutr 104: 434-443, 1974.

18. Pillai SI, Subramanian SP, Kandaswamy M. Antidyslipidemic effect of a novel vanadium-3-hydroxy flavone complex in streptozotocin-induced experimental diabetes in rats. Biomedicine & Preventive Nutrition 4: 189-193, 2014.

19. Orhan N, Berkkan A, Orhan DD et al. Effects of Juniperus oxycedrus ssp. oxycedrus on tissue lipid peroxidation, trace elements (Cu, Zn, Fe) and blood glucose levels in experimental diabetes. J Ethnopharmacol 133: 759-764, 2011.

20. Lipinski B, Pretorius E. Novel pathway of ironinduced blood coagulation: implications for diabetes mellitus and its complications. Pol Arch Med Wewn 122: 115-122, 2012.

21. Aguirre L, Arias N, Macarulla MT et al. Beneficial effects of quercetin on obesity and diabetes. Open Nutraceuticals J 4: 189-198, 2011.

22. Qureshi S, Nawaz A, Udani S et al. Hypoglycaemic and hypolipidemic activities of Rauwolfia serpentina in alloxan-induced diabetic rats. IJP-International Journal of Pharmacology 5: 323-326, 2009.

23. Krishnamurthy G, Lakshman K, Pruthvi N et al. Antihyperglycemic and hypolipidemic activity of methanolic extract of Amaranthus viridis leaves in experimental diabetes. Indian J Pharmacol 43: 450, 2011.

24. Toma L, Stancu CS, Botez GM et al. Irreversibly glycated LDL induce oxidative and inflammatory state in human endothelial cells; added effect of high glucose. Biochem Biophys Res Commun 390: 877-882, 2009.

25. Rachh P, Rachh M, Ghadiya N et al. Antihyperlipidemic activity of Gymenma sylvestre R. Br. leaf extract on rats fed with high cholesterol diet. IJP-International Journal of Pharmacology 6(2): 138-141, 2010.

26. Alrawaiq NS, Abdullah A. A Review of Flavonoid Quercetin: Metabolism, Bioactivity and Antioxidant Properties. Int J Pharm Tech Res 6: 933-941, 2014.

27. Kaluza J, Madej D. Effect of iron and zinc supplementation and its discontinuation on lipid profile in rats. J Trace Elem Med Biol 28: 298-302, 2014.

28. Shirakawa T, Nakajima K, Shimomura Y et al. Comparison of the effect of post-heparin and pre-heparin lipoprotein lipase and hepatic triglyceride lipase on remnant lipoprotein metabolism. Clin Chim Acta 440: 193-200, 2015.

29. Shen W-J, Liang Y, Wang J et al. Regulation of hormone-sensitive lipase in islets. Diabetes Res Clin Pract 75: 14-26, 2007.

30. Imessaoudene A, Merzouk H, Berroukeche F et al. Beneficial effects of quercetin–iron complexes on serum and tissue lipids and redox status in obese rats. J Nutr Biochem 29: 107-115, 2016.

31. Sztalryd C, Kraemer FB. Differences in hormone-sensitive lipase expression in white adipose tissue from various anatomic locations of the rat. Metabolism 43: 241-247, 1994.

32. Gnoni G, Paglialonga G, Siculella L. Quercetin inhibits fatty acid and triacylglycerol synthesis in rat-liver cells. Eur J Clin Invest 39: 761-768, 2009.

33. Fargion S, Mattioli M, Fracanzani AL et al. Hyperferritinemia, iron overload, and multiple metabolic alterations identify patients at risk for nonalcoholic steatohepatitis. Am J Gastroenterol 96: 2448, 2001.

34. Mulvihill EE, Huff MW. Protection from metabolic dysregulation, obesity, and atherosclerosis by citrus flavonoids: activation of hepatic PGC1α-mediated fatty acid oxidation. PPAR research 2012: 1-9, 2012.

35. Boots AW, Haenen GR, Bast A. Health effects of quercetin: from antioxidant to nutraceutical. Eur J Pharmacol 585: 325-337, 2008.

36. Mahesh T, Menon VP. Quercetin allievates oxidative stress in streptozotocin-induced diabetic rats. Phytother Res 18: 123-127, 2004.

37. Pandey KB, Rizvi SI. Protection of protein carbonyl formation by quercetin in erythrocytes subjected to oxidative stress. Med Chem Res 19: 186-192, 2010.

38. Yokoyama A, Yokoyama A, Sakakibara H et al. Quercetin metabolites and protection against peroxynitrite-induced oxidative hepatic injury in rats. Free Radic Res 43: 913-921, 2009.

39. Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life Sci 84: 705-712, 2009.

40. Liu Y, Guo M. Studies on transition metal-quercetin complexes using electrospray ionization tandem mass spectrometry. Molecules 20: 8583-8594, 2015.

41. Memişoǧulları R, Bakan E. Levels of ceruloplasmin, transferrin, and lipid peroxidation in the serum of patients with Type 2 diabetes mellitus. J Diabetes Complications 18: 193-197, 2004.

42. Kamal M, Salem M, Kholousi N et al. Evaluation of trace elements and Malondialdehyde levels in type II diabetes mellitus. Diabetes Metab Syndr 3: 214-218, 2009.

43. Forte G, Bocca B, Peruzzu A et al. Blood metals concentration in type 1 and type 2 diabetics. Biol Trace Elem Res 156: 79-90, 2013.

44. Vayenas D, Repanti M, Vassilopoulos A et al. Influence of iron overload on manganese, zinc, and copper concentration in rat tissues in vivo: study of liver, spleen, and brain. Int J Clin Lab Res 28: 183-186, 1998.

45. SandstroÈm B. Micronutrient interactions: effects on absorption and bioavailability. Br J Nutr 85: S181-S185, 2001.

46. Johnson WT, Evans GW. Effects of the interrelationship between dietary protein and minerals on tissue content of trace metals in streptozotocin-diabetic rats. J Nutr 114: 180-190, 1984.

47. Raz I, Adler J, Havivi E. Altered tissue content of trace metals in diabetic hyperinsulinaemic sand rats (psammomys obesus). Diabetologia 31: 329-333, 1988.

48. Elamin A, Tuvemo T. Magnesium and insulindependent diabetes mellitus. Diabetes Res Clin Pract 10: 203-209, 1990.

49. Ganugapati J, Mukkavalli S, Sahithi A. Docking studies of green tea flavonoids as insulin mimetics. Inter J Comp App 30: 48-52, 2011.

50. Selvaraj S, Krishnaswamy S, Devashya V et al. Flavonoid–metal ion complexes: a novel class of therapeutic agents. Med Res Rev 34: 677-702, 2014.

Romanian Journal of Diabetes Nutrition and Metabolic Diseases

The Journal of Romanian Society of Diabetes Nutrition and Metabolic Diseases

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