NEPHROPROTECTIV EFFECTS OF CANDESARTAN ON DIABETIC NEPHROPATHY IN RATS

  • Jasmina Trojacanec Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss Cyril and Methodius University in Skopje, North Macedonia
  • Kristina Pavlovska Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Kalina Gjorgjievska Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Nikola Kolovchevski Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Emilija Shikole Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Bojan Labachevski Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Aleksandar Nikodinovski Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Igor Kikerkov Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia
  • Dimche Zafirov Department of Preclinical and Clinical Pharmacology and Toxicology, Faculty of Medicine, Ss. Cyril and Methodius University in Skopje, North Macedonia

Abstract

Diabetic nephropathy (DN) stands out as a primary contributor to end-stage kidney damage. The renin-angiotensin system (RAS) plays a pivotal role in the advancement of DN, making angiotensin receptor blockers (ARBs) particularly noteworthy due to their influence on angiotensin II in DN development. This study investigated the impact of the angiotensin receptor blocker candesartan (CAN) on rats with streptozotocin (STZ)-induced DN, characterized by albuminuria, renal hypertrophy, and mild glomerulosclerosis. DN was induced in normotensive Wistar rats through a single injection of STZ (60 mg/kg ip). STZ administration led to diabetes mellitus (DM) symptoms and DN indicators, such as poor general condition, weight loss, increased kidney weight, elevated serum creatinine levels and BUN, augmented diuresis, and notable albuminuria. These manifestations were prominent at 4 weeks, intensifying further at 8 and 12 weeks post-STZ injection. Commencing candesartan treatment (5 mg/kg BW) at the 4-week mark post-STZ injection significantly alleviated all DN symptoms, reducing serum creatinine values and BUN, albuminuria, and diuresis. Histopathological examination at 8 and 12 weeks revealed that candesartan effectively mitigated glomerulopathy progression, improved the glomerulosclerotic index, and attenuated renal histological abnormalities induced by STZ. In conclusion, candesartan treatment ameliorates STZ-induced nephropathic changes in DM rats.


 Key words: Diabetic Nephropathy, streptozotocin, candesartan, Glomerulosclerosis, Rats.


 

References

1. Jensen T, Borch-Johnsen K, Kofoed-Enevoldsen A, Deckert T. Coronary heart disease in young Type 1 (insulin-dependent) diabetic patients with and without diabetic nephropathy: incidence and risk-factors. Diabetologia 1987; 30:144-148.
2. Borch-Johnsen K, Kreiner S. Proteinuria: value as predictor of cardiovascular mortality in insulin dependent diabetes mellitus. Br Med J 1987; 294:1651-1654.
3. Parving H-H, Osterby R, Ritz E. Diabetic nephropathy. In: Brenner BM, Levine S, editors. The Kidney. Philadelphia: WB Saunders, 2000; 1731-1773.
4. Rincon-Choles H, Kasinath BS, Gorin Y, Abboud HE. Angiotensin II and growth factors in the pathogenesis of diabetic nephropathy. Kidney Int 2002; 82 (Supp l): S8-S11.
5. Berl T. Angiotensin-converting enzyme inhibitors versus AT1 receptor antagonist in cardiovascular and renal protection: The case for AT1 receptor antagonist. J Am Soc Nephrol 2004; 15(Supp l): S71-S76.
6. Deferrari G, Ravera M, Deferrari L, Vettoretti S, Ratto E, Parodi D. Renal and cardiovascular protection in type 2 diabetes mellitus: Angiotensin II receptor blockers. J Am Soc Nephrol 2002; 13(Supp l3): S224-S229.
7. Lasaridis AN, Sarefidis PA. Diabetic nephropathy and antihy-pertensive treatment: what are the lessons from clinical trials? Am J Hypertens. 2003; 16:689-97.
8. Xi XP, Graf K, Goetze S, Fleck E, Hsueh WA, Law RE. Central role of the MAPK pathway in ang II-mediated DNA synthesis and migration in rat vascular smooth muscle cells. Arterioscler Thromb Vasc Biol 19: 73–82, 1999.
9. Jackson B, Franze L, Whitty M. Systemic and renovascular hypertension. Tohoku J Exp Med 1992; 166: 155 –164.
10. Dworkin LD, Feiner HD, Parker M, Tolbert E. Effects of nifedipine and enalapril on glomerular structure and function in uninephrectomized SHR. Kidney Int 1991; 39: 1112 –1117.
11. Weir MR. Hypertensive nephropathy: Is a more physiologic approach to blood pressure control an important concern for the preservation of renal function? Am J Med 1992; 93: 27S –37S.
12. Eddy AA. Molecular basis of renal fibrosis. Pediatr Nephrol 2000; 15: 290 –301.
13. Erwig LP, Kluth DC, Rees AJ. Macrophages in renal inflammation. Curr Opin Nephrol Hypertens 2001; 10: 341 –347.
14. Ridker PM, Hennekens CH, Buring JE, Rifai N: C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836 –843.
15. Schulz R, Heusch G. Angiotensin II type 1 receptors in cerebral ischaemia-reperfusion. Initiation of inflammation. J Hypertens 2006; Suppl 24: S123 –S129.
16. Brenner BM, Cooper ME, de Zeeuw D, Keane WF, Mitch WE, Parving HH, et al. RENAAL Study Investigators: Effects of losartan on renal and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001; 345: 861-869.
17. Lewis EJ, Hunsicker LG, Clarke WR, Berl T, Pohl MA, Lewis JB, et al. Collaborative Study Group: Renoprotective effect of the angiotensinreceptor antagonist irbesartan in patients with nephropathy due to type 2 diabetes. N Engl J Med 2001; 345: 851-860.
18. Parving HH, Lehnert H, Bröchner-Mortensen J, Gomis R, Andersen S, Arner P, et al. The effect of irbesatan on the developmnet of diabetic nephropathy in patients with type 2 diabetes. N Engl J Med 2001; 345: 870-878.
19. Saito T, Sumithran E, Glasgow EF, Atkins RC. The enhancement of aminonucleoside nephrosis by the co-administration of protamine. Kidney Int 1987; 32: 691–699.
20. Kilaru P, Bakris GL. Microalbuminuria and progressive renal disease. J Hum Hypertens 1994; 8: 809–817.
21. Hostetter TH, Troy JL, Brenner BM. Glomerular hemodynamics in experimental diabetes mellitus.Kidney Int. 1981; 19(3): 410-5.
22. Brenner BM, Meyer TW, Hostetter TH. Dietary protein intake and the progressive nature of kidney disease: the role of hemodynamically mediated glomerular injury in the pathogenesis oprogressiveglomerular sclerosis in aging, renal ablation, and intrinsic renal disease.N Engl J Med. 1982; 307(11): 652-9
23. Anderson S, Rennke HG, Brenner BM. Therapeutic advantage of converting enzyme inhibitors in arresting progressive renal disease associated with systemic hypertension in the rat. J Clin Invest. 1986; 77(6):1993-2000.
24. Huang XR, Chen WY, Truong LD, Lan HY. Chymase is upregulated in diabetic nephropathy: Implications for an alternative pathway of angiotensin ΙΙ mediated diabetic renal and vascular disease. J Am Soc Nephrol. 2003; 14:1738-47.
25. Cooper ME. Interaction of metabolic and haemodynamic factors in mediating experimental diabetic nephropathy. Diabetologia. 2001; 44:1957-72.
26. Nevin E. Selma Y. Melek O, Matem T et al. Effects of ACE inhibition on the expression of type IV collagen and laminin in renal glomeruli in experimental diabetes. Acta Histochemica 2004; 106 (4): 279-287.
27. Huang W, Yves G, Nadine B, Patrick B, Didier H, Pierre M et al. Genetically increased angiotensin I converting enzyme level and renal complications in the diabetic mouse. Proc Natl Acad Sci USA, 2001; 98(23):13330-34.
Published
2023-12-26
How to Cite
TROJACANEC, Jasmina et al. NEPHROPROTECTIV EFFECTS OF CANDESARTAN ON DIABETIC NEPHROPATHY IN RATS. Journal of Morphological Sciences, [S.l.], v. 6, n. 3, p. 21-33, dec. 2023. ISSN 2545-4706. Available at: <http://jms.mk/jms/article/view/vol6no3-4>. Date accessed: 01 apr. 2025.
Citation Formats
Issue
Vol 6 No 3 (2023): JMS
Section
Articles