COMBINATION EFFECT OF LISINOPRIL AND DILTIAZEM AS ANTI FIBROSIS IN PERITONEUM OF RATS

  • Wachid Putranto Student of Doctoral Programme, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia.
  • Imam Effendi Department of Internal Medicine,Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia.
  • Kusmardi Kusmardi Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
  • Hamzah Shatri Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.

Abstract

 Objective: The objective of this research was to evaluate the effect of combination between lisinopril and diltiazem in reducing expression of transforming growth factor-β (TGF-β) and fibrosis peritoneum in a male rat treated with continuous ambulatory peritoneal dialysis (CAPD).

Method: This was an experimental study, post-test only control group design. Thirsty Dawley Sprague rats are divided into five groups: Control group (Group 1), CAPD liquid 4,25% (Group 2), lisinopril 1.44 mg oral and CAPD (Group 3), and diltiazem CD 6.48 mg oral and CAPD (Group 4), lisinopril 1.44 mg+diltiazem CD 6.48 mg oral and CAPD (Group 5). After 4 weeks, rats sacrificed expression of TGF-β and peritoneal fibrosis are conducted by histopathology with hematoxylin-eosin staining and immunology with anti-human-TGF-β.

Result: Twenty peritoneal of rats can be examined. Mean score of TGF-β in control group is 1, 8, in CAPD group is 2, in lisinopril and CAPD group is 1, 8, in diltiazem CD and CAPD group is 1, 8, in lisinopril and diltiazem CD and CAPD group is 1, 7 (p=0.959). Mean score of peritoneal fibrosis in control group is 1, 1, in CAPD group is 2, 6, in lisinopril and CAPD group is 1, 2, in diltiazem CD and CAPD group is 1, 3, in lisinopril and diltiazem CD, and CAPD group is 1, 5 (p=0,268).

Conclusion: Combination of lisinopril and diltiazem lower the expression of TGF-β and peritoneum fibrosis better than lisinopril or diltiazem but statistically not significant. Combination of lisinopril and diltiazem lower the peritoneal fibrosis but statistically not significant, and it does not better than lisinopril or diltiazem.

Keywords: Angiotensin converting enzyme inhibitor, Calcium channel blocker, Transforming growth factor-β, Peritoneal fibrosis.

Author Biographies

Wachid Putranto, Student of Doctoral Programme, Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia.
Internal Medicine
Imam Effendi, Department of Internal Medicine,Faculty of Medicine, Sebelas Maret University, Surakarta, Indonesia.
Anatomical pathology
Kusmardi Kusmardi, Department of Anatomical Pathology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Internal Medicine
Hamzah Shatri, Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Internal medicine

References

1. Aroeira LS, Aguilera A, Sánchez-Tomero JA, Bajo MA, del Peso G, Jiménez-Heffernan JA, et al. Epithelial to mesenchymal transition and peritoneal membrane failure in peritoneal dialysis patients: Pathologic significance and potential therapeutic interventions. J Am Soc Nephrol 2007;18:2004-13.
2. Kyuden Y, Ito T, Masaki T, Yorioka N, Kohno N. Tgf-beta1 induced by high glucose is controlled by angiotensin-converting enzyme inhibitor and angiotensin II receptor blocker on cultured human peritoneal mesothelial cells. Perit Dial Int 2005;25:483-91.
3. Del Peso G, Jiménez-Heffernan JA, Bajo MA, Aroeira LS, Aguilera A, Fernández-Perpén A, et al. Epithelial-to-mesenchymal transition of mesothelial cells is an early event during peritoneal dialysis and is associated with high peritoneal transport. Kidney Int Suppl 2008;108:S26-33.
4. Duman S, Günal AI, Sen S, Asçi G, Ozkahya M, Terzioglu E, et al. Does enalapril prevent peritoneal fibrosis induced by hypertonic (3.86%) peritoneal dialysis solution? Perit Dial Int 2001;21:219-24.
5. Fang CC, Yen CJ, Chen YM, Chu TS, Lin MT, Yang JY, et al. Diltiazem suppresses collagen synthesis and IL-1beta-induced TGF-beta1 production on human peritoneal mesothelial cells. Nephrol Dial Transplant 2006;21:1340-7.
6. Schilte MN, Celie JW, Wee PM, Beelen RH, van den Born J. Factors contributing to peritoneal tissue remodeling in peritoneal dialysis. Perit Dial Int 2009;29:605-17.
7. Sukandar E. Clinical Nephrology. Bandung: Faculty of Medicine, Pajajaran University; 2006. p. 465-529.
8. Sculman G, Himmelfarb J. Hemodialysis. In: Brenner B, Braunwald E, Fauci AS, editors. The Kidney. 7th ed. Philadelphia, PA: Saunders Elseviers; 2004. p. 1663-8, 19610.
9. Kolesnyk I, Dekker W, Noordzij M. Impact of ACE inhibitors and all receptors blockers on peritoneal membrane transport characteristics in long term peritoneal dialysis patients. Perit Dial Int 2007;27:446-53.
10. Kitiyakara C, Yamwong S, Vathesatogkit P, Chittamma A, Cheepudomwit S, Vanavanan S, et al. The impact of different GFR estimating equations on the prevalence of CKD and risk groups in a southeast asian cohort using the new KDIGO guidelines. BMC Nephrol 2012;13:1.
11. Cohen EP. Chronic renal failure and dialysis. ACP Medicine. Vol. 3. New York: WebMD; 2007. p. 123-6.
12. Ross E, Carusso J. Hemodialysis and continous therapies. In: Daugirdas T, Blake G, editors. Handbook of Nephrology and Hypertension 5th ed. Philadelphia, PA: Lippicott Williams & Wilkins; 2005. p. 281-93.
13. Singh A, Brenner B. Dialysis in the treatment of renal failure. In: Kasper DL, Fauci AS, Longo DL, Braunwald E, Hauser SL, Jameson JL, editors. Harrison Principles of Internal Medicine 16th ed. New York: McGraw-Hill Companies Inc; 2006. p. 1663-8.
14. Nakamura S, Niwa T. Advanced glycation end-products and peritoneal sclerosis. Semin Nephrol 2004;24:502-5.
15. Guo H, Leung JC, Lam MF, Chan LY, Tsang AW, Lan HY, et al. Smad7 transgene attenuates peritoneal fibrosis in uremic rats treated with peritoneal dialysis. J Am Soc Nephrol 2007;18:2689-703.
16. Margetts PJ, Bonniaud P. Basic mechanisms and clinical implications of peritoneal fibrosis. Perit Dial Int 2003;23:530-41.
17. Kihm LP, Müller-Krebs S, Klein J, Ehrlich G, Mertes L, Gross ML, et al. Benfotiamine protects against peritoneal and kidney damage in peritoneal dialysis. J Am Soc Nephrol 2011;22:914-26.
18. Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: Sparking the development of diabetic vascular injury. Circulation 2006;114:597-605.
19. Cheng L, Tang Y, Zheng D. Advanced glycation end-products activate the renin angiotensin system through the RAGE/P13-K signaling pathway in podocytes. Clin Ivest Med 2012;35:E282-93.
20. Basta G, Schmidt AM, De Caterina R. Advanced glycation end products and vascular inflammation: Implications for accelerated atherosclerosis in diabetes. Cardiovasc Res 2004;63:582-92.
21. Hill JJ, Tremblay TL, Cantin C, O’Connor-McCourt M, Kelly JF, Lenferink AE, et al. Glycoproteomic analysis of two mouse mammary cell lines during transforming growth factor (TGF)-beta induced epithelial to mesenchymal transition. Proteome Sci 2009;7:2.
22. Letterio JJ, Roberts AB. Regulation of immune responses by TGF-beta. Annu Rev Immunol 1998;16:137-61.
23. Blobe G, Schiemann W, Lodish H. Role of transforming growth factor ß in human disease. N Engl J Med 2000;343:228.
24. Daopin S, Piez KA, Ogawa Y, Davies DR. Crystal structure of transforming growth factor-beta 2: An unusual fold for the superfamily. Science 1992;257:369-73.
25. Taipale J, Saharinen J, Keski-Oja J. Extracellular matrix-associated transforming growth factor-beta: Role in cancer cell growth and invasion. Adv Cancer Res 1998;75:87-134.
26. Chen S, Jim B, Ziyadeh FN. Diabetic nephropathy and transforming growth factor-beta: Transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol 2003;23:532-43.
27. Papagianni A, Kalovoulos M, Kirmizis D, Vainas A, Belechri AM, Alexopoulos E, et al. Carotid atherosclerosis is associated with inflammation and endothelial cell adhesion molecules in chronic haemodialysis patients. Nephrol Dial Transplant 2003;18:113-9.
28. Pennison M, Pasche B. Targeting transforming growth factor-β signaling. Curr Opin Oncol 2008;19:579-85.
29. Oates J, Brown N. Antihypertensive agents and drugs therapy of hypertension In: Hardman JG, Gilman AG, editors. The Pharmacological Basis of Theurapeutics. 10th ed. New York: McGraw-Hill; 2001. p. 336-42.
30. Kostova E, Jovanoska E, Zafirov D, Jakovski K, Maleska V, Slaninka-Miceska M, et al. Dual inhibition of angiotensin converting enzyme and neutral endopeptidase produces effective blood pressure control in spontaneously hypertensive rats. Bratisl Lek Listy 2005;106:407-11.
31. Klabunde R. Cardiovasculary Physiology Concepts. Available from: http://www.cvphysiology.com/Blood/20 Pressure/BP001.htm. [Last cited on 2007 Nov 07].
32. Taddei S, Virdis A, Ghadom L, Sudono I, Salvetti A. Effects anti hypertensive drugs on endothelial dysfunction. Drugs 2002;62:265-84.
33. Hajjar I, Kotchen TA. Trends in prevalence, awareness, treatment, and control of hypertension in the united states, 1988-2000. JAMA 2003;290:199-206.
34. Sica D. Patophysiologi. In: Black HR, Elliot WJ, editors. Hypertension: A companion to Braunwald’s heart disease. 1st ed. New York: WB Saunders Company; 2007. p. 239-53.
35. Kaplan NM.Treatment of hypertention: Drugs therapy. In: Neal W, editor. Kaplan’s Clinical Hypertension. 10th ed. Philadelphia: Lippincott Williams & Wilkins; 2010. p. 198-210.
36. Supranto J. Sampling Technique for Survey and Experiment. Jakarta: PT Rineka Cipta; 2007.
37. Kuntoro. Introduction for Sampling Techniques. Surabaya: Directorate of Research Airlangga University; 1994.
38. Zainuddin M. Research Design. Surabaya: Directorate of Research Airlangga University; 1999.
39. Tomino Y. Enzyme Antibody Method. In Laboratory Techniques in Renal Cell and Molecular Biology. Tokyo, Japan: Bunkodo Co, Ltd; 2000. p. 82-93.
40. Duman S, Sen S, Duman C, Oreopoulos DG. Effect of valsartan versus lisinopril on peritoneal sclerosis in rats. Int J Artif Organs 2005;28:156-63.
41. Bodenham T, Topley N, Fraser D. Peritoneal fibrosis is mouse strain dependent. Nephrol Dial Transplant 2012;27:1-3.
42. Dhodi JB, Mestry SN, Juvekar AR. Diabetic nephropathy-genesis, prevention and treatment. Int J Phar Pharm Sci 2014;6:42-7.
43. Kandavelu S, Somasundaram PC, John B, Rajendran R. Pro-inflammatory cytokines elicit inflammatory response in blood leukocytes of post dialytic chronic renal patients through heme oxygenase-1 activation. Int J Pharm Pharm Sci 2014;6:111-5.
44. Ersoy R, Celik A, Yilmaz O,Sarioglu S, Sis B, Akan P, et al. The effects of irbesartan anf spironolactone in prevention of peritoneal fibrosis in rats. Perit Dial Int 2007;27:4.
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Putranto, W., I. Effendi, K. Kusmardi, and H. Shatri. “COMBINATION EFFECT OF LISINOPRIL AND DILTIAZEM AS ANTI FIBROSIS IN PERITONEUM OF RATS”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 3, Mar. 2018, pp. 71-76, doi:10.22159/ajpcr.2018.v11i3.23152.
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