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Attenuation of oxidative stress and cardioprotective effects of zinc supplementation in experimental diabetic rats

  • Susmita Barman (a1) and Krishnapura Srinivasan (a1)

Abstract

Oxidative stress plays a major role in the pathogenesis of diabetes mellitus, which further exacerbates damage of cardiac, hepatic and other tissues. We have recently reported that Zn supplementation beneficially modulates hyperglycaemia and hypoinsulinaemia, with attendant reduction of associated metabolic abnormalities in diabetic rats. The present study assessed the potential of Zn supplementation in modulating oxidative stress and cardioprotective effects in diabetic rats. Diabetes was induced in Wistar rats with streptozotocin, and groups of diabetic rats were treated with 5- and 10-fold dietary Zn interventions (0·19 and 0·38 g Zn/kg diet) for 6 weeks. The markers of oxidative stress, antioxidant enzyme activities and concentrations of antioxidant molecules, lipid profile, and expressions of fibrosis and pro-apoptotic factors in the cardiac tissue were particularly assessed. Supplemental Zn showed significant attenuation of diabetes-induced oxidative stress in terms of altered antioxidant enzyme activities and increased the concentrations of antioxidant molecules. Hypercholesterolaemia and hyperlipidaemia were also significantly countered by Zn supplementation. Along with attenuated oxidative stress, Zn supplementation also showed significant cardioprotective effects by altering the mRNA expressions of fibrosis and pro-apoptotic factors (by >50 %). The expression of lipid oxidative marker 4-hydroxy-2-nonenal (4-HNE) protein in cardiac tissue of diabetic animals was rectified (68 %) by Zn supplementation. Elevated cardiac and hepatic markers in circulation and pathological abnormalities in cardiac and hepatic tissue architecture of diabetic animals were ameliorated by dietary Zn intervention. The present study indicates that Zn supplementation can attenuate diabetes-induced oxidative stress in circulation as well as in cardiac and hepatic tissues.

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Corresponding author

* Corresponding author: Dr K. Srinivasan, fax +91 821 251 7233, email ksri.cftri@gmail.com

References

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1. Sharma, P, Jha, A, Dubey, RS, et al. (2012) Reactive oxygen species, oxidative damage, and antioxidativedefense mechanism in plants under stressful conditions. J Botany 2012, e217037.
2. Bandyopadhyay, U, Das, D & Banerjee, RK (1999) Reactive oxygen species: oxidative damage and pathogenesis. Curr Sci 77, 658666.
3. Hruda, J, Sramek, V & Leverve, X (2010) High glucose increases susceptibility to oxidative-stress-induced apoptosis and DNA damage in K-562 cells. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub 154, 315320.
4. Saxena, AK, Srivastava, P, Kale, RK, et al. (1993) Impaired antioxidant status in diabetic rat liver: effect of vanadate. Biochem Pharmacol 45, 539542.
5. De Marchi, E, Baldassari, F, Bononi, A, et al. (2013) Oxidative stress in cardiovascular diseases and obesity: role of p66Shc and protein kinase C. Oxid Med Cell Longev 2013, e564961.
6. Foster, M & Samman, S (2010) Zinc and redox signaling: perturbations associated with cardio vascular disease and diabetes mellitus. Antioxid Redox Signal 13, 15491573.
7. Chausmer, AB (1998) Zinc, insulin and diabetes. J Am Coll Nutr 17, 109115.
8. Barman, S & Srinivasan, K (2016) Zinc supplementation alleviates hyperglycemia and associated metabolic abnormalities in streptozotocin-induced diabetic rats. Can J Physiol Pharmacol 94, 13561365.
9. Prasad, AS (2008) Zinc in human health: effect of zinc on immune cells. Mol Med 14, 353357.
10. Prasad, AS (2013) Biochemistry of Zinc. New York: Springer Science & Business Media.
11. Jayawardena, R, Ranasinghe, P, Galappatthy, P, et al. (2012) Effects of zinc supplementation on diabetes mellitus: a systematic review and meta-analysis. Diabetol Metab Syndr 4, 13.
12. Huggett, AS & Nixon, DA (1957) Use of glucose oxidase, peroxidase, and o-dianisidine in determination of blood and urinary glucose. Lancet 273, 368370.
13. LeBel, CP, Ischiropoulos, H & Bondy, SC (1992) Evaluation of the probe 2',7'-dichloro fluorescin as an indicator of reactive oxygen species formation and oxidative stress. Chem Res Toxicol 5, 227231.
14. Driver, AS, Kodavanti, PR & Mundy, WR (2000) Age-related changes in reactive oxygen species production in rat brain homogenates. Neurotoxicol Teratol 22, 175181.
15. Yagi, K (1984) Assay for blood plasma or serum. Methods Enzymol 105, 328331.
16. Ohkawa, H, Ohishi, N & Yagi, K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95, 351358.
17. Reznick, AZ & Packer, L (1994) Oxidative damage to proteins: spectrophotometric method for carbonyl assay. Methods Enzymol 233, 357363.
18. Flohé, L & Otting, F (1984) Superoxide dismutase assays. Methods Enzymol 105, 93104.
19. Aebi, H (1984) Catalase in vitro . Methods Enzymol 105, 121126.
20. Flohé, L & Günzler, WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105, 114121.
21. Carlberg, I & Mannervik, B (1985) Glutathione reductase. Methods Enzymol 113, 484490.
22. Warholm, M, Guthenberg, C, von Bahr, C, et al. (1985) Glutathione transferases from human liver. Methods Enzymol 113, 499504.
23. Beutler, E, Duron, O & Kelly, BM (1963) Improved method for the determination of blood glutathione. J Lab Clin Med 61, 882888.
24. Omaye, ST, Turnbull, JD & Sauberlich, HE (1979) Selected methods for the determination of ascorbic acid in animal cells, tissues, and fluids. Methods Enzymol 62, 311.
25. Kind, PRN & King, EJ (1954) Estimation of plasma phosphatase by determination of hydrolysed phenol with amino-antipyrine. J Clin Pathol 7, 322326.
26. Lowry, OH, Rosebrough, NJ, Farr, AL, et al. (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193, 265275.
27. Folch, J, Lees, M & Stanley, GHS (1957) A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 226, 497509.
28. Searcy, RL & Bergquist, LM (1960) A new color reaction for the quantitation of serum cholesterol. Clin Chim Acta 5, 192199.
29. Warnick, GR & Albers, JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein cholesterol. J Lipid Res 19, 6576.
30. Stewart, JCM (1980) Colorimetric determination of phospholipids with ammonium ferro thiocyanate. Anal Biochem 104, 1014.
31. Fletcher, MJ (1968) A colorimetric method for estimating serum triglycerides. Clin Chim Acta 22, 393397.
32. Bowyer, DE, Leat, WMF, Howard, AN, et al. (1963) The determination of the fatty acid composition of serum lipids separated by thin-layer chromatography; and a comparison with column chromatography. Biochem Biophys Acta 70, 423431.
33. Suresha, BS, Vasantha, KY, Sattur, AP, et al. (2012) Beneficial influence of fungal metabolite nigerloxin on diabetes-induced oxidative stress in experimental rats. Can J Physiol Pharmacol 91, 149156.
34. Pandey, K, Mishra, N & Rizvi, SI (2010) Protein oxidation biomarkers in plasma of type 2 diabetic patients. Clin Biochem 43, 508511.
35. Maritim, AC, Sanders, RA & Watkins, JB (2003) Diabetes, oxidative stress, and antioxidants: a review. J Biochem Mol Toxicol 17, 2438.
36. Muruganandam, A, Drouillard, C, Thibert, RJ, et al. (1992) Glutathione metabolic enzyme activities in diabetic platelets as a function of glycemic control. Thromb Res 67, 385397.
37. Avendano, GF, Agarwal, RK, Bashey, RI, et al. (1999) Effects of glucose intolerance on myocardial function and collagen-linked glycation. Diabetes 48, 443447.
38. Du, X, Matsumura, T, Edelstein, D, et al. (2003) Inhibition of GAPDH Activity by poly(ADP-ribose) polymerase activates three major pathways of hyperglycemic damage in endothelial cells. J Clin Invest 112, 10491057.
39. Nishikawa, T, Edelstein, D, Du, XL, et al. (2000) Normalizing mitochondrial superoxide production blocks three pathways of hyperglycaemic damage. Nature 404, 787790.
40. Mitra, B & Panja, M (2005) Myocardial metabolism: pharmacological manipulation in myocardial ischaemia. J Assoc Physicians India 53, 552560.
41. Karagulova, G, Yue, Y, Moreyra, A, et al. (2007) Protective role of intracellular zinc in myocardial ischemia/ reperfusion is associated with preservation of protein kinase C isoforms. J Pharmacol Exp Therap 321, 517525.
42. Cyrus, T, Praticò, D, Zhao, L, et al. (2001) Absence of 12/15-lipoxygenase expression decreases lipid peroxidation and atherogenesis in apolipoprotein E-deficient mice. Circulation 103, 22772282.
43. Shokrzadeh, M, Ghaemian, A, Salehifar, E, et al. (2009) Serum zinc and copper levels in ischemic cardiomyopathy. Biol Trace Elem Res 127, 116123.
44. Bernal, PJ, Bauer, EM, Cao, R, et al. (2011) A role for zinc in regulating hypoxia-induced contractile events in pulmonary endothelium. Am J Physiol Lung Cell Mol Physiol 300, L874L886.
45. Ayala, A, Munoz, MF & Arguelles, S (2014) Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longevity 2014, May, e360438.
46. Liu, RM, Vayalil, PM, Ballinger, C, et al. (2012) Transforming growth factor Β suppresses glutamate–cysteine ligase gene expression and induces oxidative stress in a lung fibrosis model. Free Rad Biol Med 53, 554563.
47. Lee, HJ, Lee, HJ, Lee, EO, et al. (2008) Mitochondria-cytochrome C-caspase-9 cascade mediates isorhamnetin-induced apoptosis. Cancer Lett 270, 342353.
48. Srinivasan, S, Stevens, M & Wiley, JW (2000) Diabetic peripheral neuropathy: evidence for apoptosis and associated mitochondrial dysfunction. Diabetes 49, 19321938.
49. Aragno, M, Mastrocola, R, Alloatti, G, et al. (2008) Oxidative stress triggers cardiac fibrosis in the heart of diabetic rats. Endocrinology 149, 380388.
50. Haritha, C, Gopalareddy, A, Ramanareddy, Y, et al. (2013) Evaluation of protective action of fenugreek, insulin and glimepiride and their combination in diabetic sprague dawley rats. J Nat Sci Biol Med 4, 207212.
51. Shi, F, Sheng, Q, Xu, X, et al. (2015) Zinc supplementation suppresses the progression of bile duct ligation-induced liver fibrosis in mice. Exp Biol Med 240, 11971204.
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British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
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