FPS-ZM1 and valsartan combination protects better against glomerular filtration barrier damage in streptozotocin-induced diabetic rats

  • Davoud Sanajou
  • Amir Ghorbani Haghjo
  • Hassan Argani
  • Leila Roshangar
  • Saeed Nazari Soltan Ahmad
  • Zahra Ashrafi Jigheh
  • Somayeh Aslani
  • Fatemeh Panah
  • Jalil Rashedi
  • Mehran Mesgari Abbasi
Original Article

Abstract

Despite the effectiveness of renin-angiotensin blockade in retarding diabetic nephropathy progression, a considerable number of patients still develop end-stage renal disease. The present investigation aims to evaluate the protective potential of FPS-ZM1, a selective inhibitor of receptor for advanced glycation end products (RAGE), alone and in combination with valsartan, an angiotensin receptor blocker, against glomerular injury parameters in streptozotocin-induced diabetic rats. FPS-ZM1 at 1 mg/kg (i.p.), valsartan at 100 mg/kg (p.o.), and their combination were administered for 4 weeks, starting 2 months after diabetes induction in rats. Tests for kidney function, glomerular filtration barrier, and podocyte slit diaphragm integrities were performed. Combined FPS-ZM1/valsartan attenuated diabetes-induced elevations in renal levels of RAGE and phosphorylated NF-κB p65 subunit. It ameliorated glomerular injury due to diabetes by increasing glomerular nephrin and synaptopodin expressions, mitigating renal integrin-linked kinase (ILK) levels, and lowering urinary albumin, collagen type IV, and podocin excretions. FPS-ZM1 also improved renal function as demonstrated by decreasing levels of serum cystatin C. Additionally, the combination also alleviated indices of renal inflammation as revealed by decreased renal monocyte chemoattractant protein 1 (MCP-1) and chemokine (C-X-C motif) ligand 12 (CXCL12) expressions, F4/80-positive macrophages, glomerular TUNEL-positive cells, and urinary alpha-1-acid glycoprotein (AGP) levels. These findings underline the benefits of FPS-ZM1 added to valsartan in alleviating renal glomerular injury evoked by diabetes in streptozotocin rats and suggest FPS-ZM1 as a new potential adjunct to the conventional renin-angiotensin blockade.

Keywords

Diabetic nephropathy FPS-ZM1 Podocyte injury STZ-induced diabetic rats Valsartan 

Notes

Funding information

This work was supported by grants from the Biotechnology Research Center and Students’ Research Center, Tabriz University of Medical Science, and the Urology and Nephrology Research Center, Beheshti University of Medical Sciences.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© University of Navarra 2018

Authors and Affiliations

  • Davoud Sanajou
    • 1
    • 2
  • Amir Ghorbani Haghjo
    • 3
  • Hassan Argani
    • 4
  • Leila Roshangar
    • 5
  • Saeed Nazari Soltan Ahmad
    • 1
  • Zahra Ashrafi Jigheh
    • 1
  • Somayeh Aslani
    • 1
  • Fatemeh Panah
    • 1
  • Jalil Rashedi
    • 1
  • Mehran Mesgari Abbasi
    • 6
  1. 1.Department of Biochemistry, Faculty of MedicineTabriz University of Medical SciencesTabrizIran
  2. 2.Student Research CenterTabriz University of Medical SciencesTabrizIran
  3. 3.Biotechnology Research CenterTabriz University of Medical SciencesTabrizIran
  4. 4.Urology and Nephrology Research CenterBeheshti University of Medical SciencesTehranIran
  5. 5.Stem Cell Research CenterTabriz University of Medical SciencesTabrizIran
  6. 6.Drug Applied Research CenterTabriz University of Medical SciencesTabrizIran

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