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Alam MA, Chowdhury MRH, Jain P, et al. DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats. Diabetol Metab Syndr. 2015;7:107doi: 10.1186/s13098-015-0095-3.
Alam, M. A., Chowdhury, M. R. H., Jain, P., Sagor, M. A. T., & Reza, H. M. (2015). DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats. Diabetology & metabolic syndrome, 7107. https://doi.org/10.1186/s13098-015-0095-3
Alam, Md Ashraful, et al. "DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats." Diabetology & metabolic syndrome vol. 7 (2015): 107. doi: https://doi.org/10.1186/s13098-015-0095-3
Alam MA, Chowdhury MRH, Jain P, Sagor MAT, Reza HM. DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats. Diabetol Metab Syndr. 2015 Nov 25;7:107. doi: 10.1186/s13098-015-0095-3. eCollection 2015. PMID: 26609328; PMCID: PMC4658771.
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Diabetol Metab Syndr. 2015 Nov 25;7:107. doi: 10.1186/s13098-015-0095-3. eCollection 2015.

DPP-4 inhibitor sitagliptin prevents inflammation and oxidative stress of heart and kidney in two kidney and one clip (2K1C) rats.

Diabetology & metabolic syndrome

Md Ashraful Alam, Mohammed Riaz Hasan Chowdhury, Preeti Jain, Md Abu Taher Sagor, Hasan Mahmud Reza

Affiliations

  1. Department of Pharmaceutical Sciences, School of Life Sciences, North South University, Bashundhara, Dhaka, Bangladesh.

PMID: 26609328 PMCID: PMC4658771 DOI: 10.1186/s13098-015-0095-3

Abstract

BACKGROUND: Hyperglycemia and insulin resistance often develop cardiovascular and nephrological dysfunction in diabetic patients. Sitagliptin is used to treat diabetes and showed potential benefit in lowering increased blood glucose level in diabetes. This investigation reports the effect of sitagliptin treatment on oxidative stress in kidney and heart of 2K1C rats.

METHODS: Male Long Evans rats underwent unilateral surgical stenosis of the renal artery [2-kidney-1-clip (2K1C) method]. These animals entered a 4-weeks dosing period with sitagliptin. Blood and urine sampling and organ harvesting were finally performed. Blood plasma, heart, kidney tissues and urine were tested for the assessment of inflammation and oxidative stress in kidney and heart of 2K1C rats after 4 weeks of surgery.

RESULTS: 2K1C rats showed cardiac hypertrophy, increased left ventricular wet weight compared to sham which was not significantly altered by sitagliptin treatment. Uric acid and creatinin concentrations were also increased in 2K1C rats. Sitagliptin significantly prevented the elevation of uric acid and creatinin concentration in plasma and urine in this rat model. Oxidative stress markers in plasma such as malondialdehyde (MDA), nitric oxide (NO), and advanced protein oxidation product (APOP) concentrations were increased in the 2K1C rats as compared to sham-operated animals. Increased concentrations of these oxidative stress markers were also normalized by sitagliptin treatment. 2K1C rats also showed increased level of uric acid and creatinine both in plasma and urine; which are also reduced to normal level in sitagliptin treated rats. Moreover, 2K1C surgery initiated inflammatory cell infiltration, increased MPO activity and fibrosis in both heart and kidneys which were further ameliorated by sitagliptin treatment.

CONCLUSION: Our study suggests that sitagliptin treatment in 2K1C rats prevented inflammation and fibrosis of heart and kidney by ameliorating elevated oxidative stress in heart and kidney tissues.

Keywords: Fibrosis; Inflammation; Malondialdehyde; Oxidative stress; Sitagliptin

References

  1. J Am Soc Nephrol. 2000 Sep;11(9):1656-66 - PubMed
  2. Hypertens Res. 2007 May;30(5):439-49 - PubMed
  3. Nurse Pract. 2014 Aug 16;39(8):22-32; quiz 32-3 - PubMed
  4. Hypertension. 1980 May-Jun;2(3):256-65 - PubMed
  5. Hypertension. 2010 Oct;56(4):728-33 - PubMed
  6. J Am Coll Cardiol. 2006 Jul 4;48(1):97-8 - PubMed
  7. N Engl J Med. 2002 Jun 20;346(25):1954-62 - PubMed
  8. Hypertension. 2002 Oct;40(4):477-84 - PubMed
  9. Diabetes Care. 2014 Jan;37 Suppl 1:S14-80 - PubMed
  10. Braz J Med Biol Res. 2015 Jan;48(1):65-76 - PubMed
  11. Kidney Int. 1996 May;49(5):1304-13 - PubMed
  12. Heart. 2007 Aug;93(8):903-7 - PubMed
  13. Hypertension. 2002 Feb;39(2 Pt 2):316-22 - PubMed
  14. Circulation. 1998 Apr 28;97(16):1536-9 - PubMed
  15. Eur J Biochem. 1968 Oct 17;6(1):126-30 - PubMed
  16. ISRN Pharmacol. 2014 Mar 04;2014:608590 - PubMed
  17. Hypertens Res. 2014 Jan;37(1):43-9 - PubMed
  18. Endocrinology. 2013 Jul;154(7):2501-13 - PubMed
  19. Diabetologia. 2009 Apr;52(4):691-7 - PubMed
  20. Mol Cell Endocrinol. 2009 Apr 29;302(2):148-58 - PubMed
  21. Am J Nephrol. 2008;28(4):548-54 - PubMed
  22. Diabetes Care. 2007 Jun;30(6):1335-43 - PubMed
  23. Exp Diabetes Res. 2011;2011:162092 - PubMed
  24. Clin Exp Pharmacol Physiol. 2003 Nov;30(11):860-6 - PubMed
  25. J Pharmacol Exp Ther. 2012 Feb;340(2):248-55 - PubMed
  26. BMC Complement Altern Med. 2012 Oct 09;12:181 - PubMed
  27. Diabetologia. 2003 Oct;46(10):1402-7 - PubMed
  28. J Invest Dermatol. 1982 Mar;78(3):206-9 - PubMed
  29. J Am Coll Cardiol. 2006 Jul 4;48(1):89-96 - PubMed
  30. Am J Physiol Regul Integr Comp Physiol. 2004 Nov;287(5):R1014-30 - PubMed
  31. Eur J Pharmacol. 2012 Mar 15;679(1-3):81-9 - PubMed
  32. J Pharmacol Exp Ther. 1995 Mar;272(3):1011-5 - PubMed
  33. Clin Sci (Lond). 2009 Mar;116(6):479-92 - PubMed
  34. Kidney Int Suppl. 2007 Aug;(106):S49-53 - PubMed
  35. Hypertension. 2006 Sep;48(3):460-6 - PubMed
  36. Kidney Int Suppl. 2000 Sep;77:S3-12 - PubMed
  37. Nephrol Dial Transplant. 2005 Nov;20(11):2420-6 - PubMed
  38. Diabetes. 2008 Jun;57(6):1446-54 - PubMed
  39. J Hum Hypertens. 2005 Apr;19(4):301-7 - PubMed
  40. Cardiovasc Res. 1998 Jul;39(1):89-105 - PubMed
  41. J Cell Mol Med. 2013 Oct;17(10):1300-7 - PubMed
  42. Am J Physiol Regul Integr Comp Physiol. 2005 Dec;289(6):R1770-6 - PubMed
  43. J Am Soc Nephrol. 2005 Mar;16 Suppl 1:S78-82 - PubMed
  44. Gastroenterology. 2002 Feb;122(2):531-44 - PubMed
  45. Circulation. 1995 Mar 15;91(6):1872-85 - PubMed
  46. J Clin Invest. 1998 Jan 1;101(1):160-9 - PubMed
  47. Hypertension. 2001 Feb;37(2 Pt 2):541-6 - PubMed
  48. Obesity (Silver Spring). 2014 Oct;22(10):2172-9 - PubMed
  49. Front Biosci (Landmark Ed). 2012 Jan 01;17:221-31 - PubMed
  50. Regul Pept. 2011 Jan 17;166(1-3):48-54 - PubMed
  51. Am J Physiol Renal Physiol. 2009 Jan;296(1):F78-86 - PubMed
  52. J Clin Hypertens (Greenwich). 2006 Dec;8(12 Suppl 4):17-29 - PubMed
  53. Hypertension. 2012 Sep;60(3):833-41 - PubMed
  54. Exp Mol Pathol. 2013 Feb;94(1):1-9 - PubMed
  55. Oxid Med Cell Longev. 2015;2015:478039 - PubMed
  56. BMC Nephrol. 2013 Apr 27;14 :98 - PubMed
  57. Pharmacology. 2010;86(4):240-8 - PubMed
  58. J Cardiovasc Pharmacol. 2013 Mar;61(3):240-9 - PubMed
  59. Cardiovasc Res. 1998 Nov;40(2):352-63 - PubMed

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