Skip to main content
SpringerLink
Log in

Selenium Downregulates Oxidative Stress-Induced Activation of Leukotriene Pathway in Experimental Rats with Diabetic Cardiac Hypertrophy

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Cardiac hypertrophy has been considered as an important risk factor of morbidity and mortality. It is characterized as thickening of ventricle wall of the heart and consequent reduction in the contracting ability of the heart to pump the blood. Hyperglycemia-induced reactive oxygen species act as major mediators of diabetic complications. Inflammation plays an essential role in the development of diabetic cardiac hypertrophy. Selenium has been shown to induce insulin-like and anti-inflammatory effects in human and experimental animals. But, its mechanism of action has not been elucidated. Hence, in order to probe into its mechanism at molecular level, we designed an experiment to study the effect of selenium as sodium selenite in streptozotocin-induced diabetic rats. The rats were divided into four groups and maintained as follows: (1) controls, (2) sodium selenite-treated controls, (3) diabetic, and (4) sodium selenite-treated diabetic rats. Duration of the experiment was 30 days. Selenium supplementation enhanced the streptozotocin-induced reduction in the activities of antioxidant enzymes, decreased the serum glucose level, glycated hemoglobin content, concentration of high-sensitivity C-reactive protein, levels of lipid peroxidation products, as well as inflammatory parameters. Decrease in the phospholipase activity by selenium supplementation also contributed to the downregulation of leukotriene pathway. It also downregulated the expressions of nuclear transcription factor κB (NFκB), lipoxygenase, cyclooxygenase, 5-lipoxygenase-activating protein, and receptor for leukotriene B4. Hence, selenium decreased the production of reactive oxygen species and inhibited the activation of NFκB-mediated transcription of pro-inflammatory mediators which resulted in the downregulation of leukotriene pathway in diabetic cardiac hypertrophy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Kuller LH, Velentgas P, Barzilay J, Beauchamp NJ, O’Leary DH, Savage PJ (2000) Diabetes mellitus subclinical cardiovascular disease and risk of incident cardiovascular disease and all cause mortality. Arterioscler Thromb Vasc Biol 20:823–829

    Article  PubMed  CAS  Google Scholar 

  2. Molkentin JD, Dorn GW (2001) Cytoplasmic signaling pathways that regulate cardiac hypertrophy. Annu Rev Physiol 63:391–426

    Article  PubMed  CAS  Google Scholar 

  3. Funk CD (2001) Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 294:1871–1875

    Article  PubMed  CAS  Google Scholar 

  4. Naziroglu M, Dilsiz N, Cay M (1999) Protective role of intraperitoneally administered vitamins C and E and selenium on the levels of lipid peroxidation in the lens of rats made diabetic with streptozotocin. Biol Trace Elem Res 70:223–232

    Article  PubMed  CAS  Google Scholar 

  5. Nazıroglu M, Karaoglu A, Orhan Aksoy A (2004) Selenium and high dose vitamin E administration protects cisplatin-induced oxidative damage to renal, liver and lens tissues in rats. Toxicology 195:221–230

    Article  PubMed  Google Scholar 

  6. Singh R, Barden A, Mori T, Beilin L (2001) Advanced glycation end-products: a review. Diabetologia 44:129–146

    Article  PubMed  CAS  Google Scholar 

  7. Rayman MP (2000) The importance of selenium to human health. Lancet 356:233–241

    Article  PubMed  CAS  Google Scholar 

  8. Taylor PR, Parnes HL, Lippman SM (2004) Science peels the onion of selenium effects on prostate carcinogenesis. J Natl Cancer Inst 96:645–647

    Article  PubMed  Google Scholar 

  9. Ghosh R, Mukherjee B, Chatterjee M (1994) A novel effect of selenium on streptozotocin-induced diabetic mice. Diabetes Res 25:165–171

    PubMed  CAS  Google Scholar 

  10. Ayaz M, Can B, Ozdemir S, Turan B (2002) Protective effect of selenium treatment on diabetes-induced myocardial structural alterations. Biol Trace Elem Res 89:215–226

    Article  PubMed  CAS  Google Scholar 

  11. Hwang D, Seo S, Kim Y et al (2007) Selenium acts as insulin like molecule for the downregulation of diabetic symptoms via endoplasmic reticulum stress and insulin signaling proteins in diabetes-induced nonobese diabetic mice. J Biosci 32:723–735

    Article  PubMed  CAS  Google Scholar 

  12. Hume CW (1972) The UFAW Handbook on the care and management of laboratory animals. Churchill Livingstone, Edinburgh

    Google Scholar 

  13. Sneha SP, Keerthi JS, Indira M (2012) Selenium downregulates RAGE and NFkB expression in diabetic rats. Biol Trace Elem Res 149:71–77

    Article  Google Scholar 

  14. Ohkawa H, Ohishi N, Yagi K (1979) Assay of lipid peroxides in animal tissue by thio barbituric acid reaction. Anal Biochem 95:351–358

    Article  PubMed  CAS  Google Scholar 

  15. John AB, Steven DA (1978) Microsomal lipid peroxidation. Methods Enzymol 52:302–310

    Article  Google Scholar 

  16. Kakkar P, Das B, Viswanathan PN (1984) A modified spectrophotometric assay of SOD. Indian J Biochem Biophys 2:130–132

    Google Scholar 

  17. Maehly AC, Chance B (1954) The assay of CAT and peroxides. Methods Biochem Anal 1:357–424

    Article  PubMed  CAS  Google Scholar 

  18. Agerguard N, Jense PT (1982) Procedure for blood glutathione peroxidase determination in cattle and swine. Acta Vet Scand 23:515–527

    Google Scholar 

  19. Brunberg JA, Halmi NS (1966) The role of ouabain-sensitive adenosine triphosphatase in the stimulating effect of thyrotropin on the iodide pump of the rat thyroid. Endocrinology 79:801–807

    Article  PubMed  CAS  Google Scholar 

  20. Richard K, Ralph S, Huch H et al (1972) Guinea pig heterophil and eosinophil peroxidase. Arch Biochem Biophys 148:452–465

    Article  Google Scholar 

  21. Rimon A, Shapiro B (1959) Properties and specificity of pancreatic phospholipase A. Biochem J 71:620

    PubMed  CAS  PubMed Central  Google Scholar 

  22. Kleiman JH, Lands WEM (1969) Purification of a phospholipase C from Bacillus cereus. Biochem Biophys Acta 187:477

    Article  PubMed  CAS  Google Scholar 

  23. Mollerung H, Bergmeyer HU (1964) In: Bergmeyer HU (ed) Methods of enzymol analysis. Academic, New York, p 415

    Google Scholar 

  24. Huch HY, Pearce SF, Yesner LM, Schindler JL, Silverstein RL (1996) Regulated expression of CD36 during monocyte-to-macrophage differentiation: potential role of CD36 in foam cell formation. Blood 87:2020–2028

    Google Scholar 

  25. Axelrod B, Cheesbrough TM, Laasko S (1981) In: Lowenstein JM (ed) Methods enzymol, vol 71., p 441

    Google Scholar 

  26. Shimizu T, Kondo K, Hayaishi O (1981) Role of prostaglandin endoperoxidases in the serum thiobarbituric acid reaction. Arch Biochim Biophys 206:271–276

    Article  CAS  Google Scholar 

  27. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    PubMed  CAS  Google Scholar 

  28. Chomczynski P, Sacchi N (2006) The single-step method of RNA isolation by acid guanidinium thiocynate-phenol-chloroform extraction: twenty-something years on. Nat Protoc 1:581–585

    Article  PubMed  CAS  Google Scholar 

  29. Bedler JL, Hilliard PR, Rill RL (1982) Identification of DNA. Anal Biochem 126:374–380

    Article  Google Scholar 

  30. Cummins LM, Kimura (1971) Safety evaluation of selenium sulfideantidandruff shampoos. Toxicol Appl Pharmacol 20:89–96

    Article  PubMed  CAS  Google Scholar 

  31. Pupim LB, Heim Burger Q, Qureshi AR, Ikizler TA, Stenvinkel P (2005) Acclerated lean body mass loss in incident chronic dialysis patients with diabetes mellitus. Kidney Int 68:2368–2374

    Article  PubMed  Google Scholar 

  32. Koenig RJ, Peterson CM, Kilo C, Cerami A, Williamson JR (1976) Hemoglobin A1c as an indicator of the degree of glucose intolerance in diabetes. Diabetes 25:230–232

    Article  PubMed  CAS  Google Scholar 

  33. Nazıroğlu M, Cay M (2001) Protective role of intraperitoneally administered vitamin E and selenium on the antioxidative defense mechanisms in rats with diabetes induced by streptozotocin. Biol Trace Elem Res 79:149–159

    Article  PubMed  Google Scholar 

  34. Kangralkar VA, Patil SD, Bandivadekar RM (2010) Oxidative stress and diabetes: a review. Int J Pharm Appl 1:38–45

    CAS  Google Scholar 

  35. Ghaffari T, Nouri M, Saei AA, Rashidi MR (2012) Aldehyde and xanthine oxidase activities in tissues of streptozotocin-induced diabetic rats: effects of vitamin E and selenium supplementation. Biol Trace Elem Res 10:9291–9297

    Google Scholar 

  36. Velavan S, Selvarani S, Adhithan A (2009) Cardioprotective effect of Trichopus zeylanicus against myocardial ischemia induced by isoproterenol in rats. Bangladesh J Pharmacol 4:88–91

    Article  Google Scholar 

  37. Zhang R, Brennan ML, Fu X et al (2001) Association between myeloperoxidase levels and risk of coronary artery disease. JAMA 286:2136–2142

    Article  PubMed  CAS  Google Scholar 

  38. Li T, Schulze M, Rifai N, Rimm E, Stampfer M, Hu F (2004) C-reactive protein and incident cardiovascular events among men with diabetes. Diabetes Care 27:889–894

    Article  PubMed  Google Scholar 

  39. Lehr M (2001) Phospholipase A2 inhibitors in inflammation. Expert Opin Ther Patents 11:1123–1136

    Article  CAS  Google Scholar 

  40. Meyers DJ, Berk RS (1990) Characterization of phospholipase C from Pseudomonas aeruginosa as a potent inflammatory agent. Infect Immun 58:659–666

    PubMed  CAS  PubMed Central  Google Scholar 

  41. Kang DW, Min G, Park do Y, Hong KW, Min do S (2010) Rebamipide-induced downregulation of phospholipase D inhibits inflammation and proliferation in gastric cancer cells. Exp Mol Med 42:555–564

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Shoeb M, Yadav UC, Srivastava SK, Ramana KV (2011) Inhibition of aldose reductase prevents endotoxin-induced inflammation by regulating arachidonic acid pathway in murine macrophages. Free Radic Biol Med 51:1686–1696

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  43. Shashkin PN, Jain N, Miller YI et al (2006) Insulin and glucose play a role in foam cell formation and function. Cardiovasc Diabetol 5:13

    Article  PubMed  PubMed Central  Google Scholar 

  44. Tabatabaie T, Waldon AM, Jacob JM, Floyd RA, Kotake Y (2000) COX-2 inhibition prevents insulin-dependent diabetes in low-dose streptozotocin-treated mice. Biochem Biophys Res Commun 273:699–704

    Article  PubMed  CAS  Google Scholar 

  45. Singal PK, Kapur N, Dhillon KS, Beamish RE, Dhalla S (1982) Role of free radicals catecholamine induced cardiomyopathy. Can J Physiol Pharmacol 60:1390–1397

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Kerala, Kariavattom, Thiruvananthapuram, 695581, Kerala, India

    B. L. Dhanya, R. P. Swathy & M. Indira

Authors
  1. B. L. Dhanya
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. R. P. Swathy
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Indira
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Indira.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dhanya, B.L., Swathy, R.P. & Indira, M. Selenium Downregulates Oxidative Stress-Induced Activation of Leukotriene Pathway in Experimental Rats with Diabetic Cardiac Hypertrophy. Biol Trace Elem Res 161, 107–115 (2014). https://doi.org/10.1007/s12011-014-0076-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12011-014-0076-7

Keywords

Search

Navigation