Treatment with irbesatan may improve slit diaphragm alterations in rats with adriamycin-induced nephropathy

J Renin Angiotensin Aldosterone Syst. 2016 May 11;17(2):1470320316646884. doi: 10.1177/1470320316646884. Print 2016 Apr-Jun.

Abstract

Objective: The study aimed to evaluate the effects of oral administration of irbesartan in adriamycin-induced nephropathy considering laboratory changes, kidney histology, and expression of proteins related to slit diaphragm and cytoskeleton of the podocyte.

Methods: The animals were divided into control, model, methylprednisolone (MP), and irbesartan groups. The 24-hour urinary protein and biochemical indicators were determined, and renal pathological changes were observed. The mRNA and protein expression of nephrin, podocin, CD2-associated protein (CD2AP), and desmin in the kidney tissue were analyzed.

Results: The urinary protein excretion levels in the MP and irbesartan groups were lower than those in the model group (p<0.01). Electron microscopy showed that fusion of the glomerular foot processes of the rats in the irbesartan group was significantly reduced. The mRNA and protein expression levels of nephrin and podocin in the renal tissue in the MP and irbesartan groups were up-regulated compared with the model group (p<0.05), whereas the mRNA and protein expression levels of CD2AP and desmin were significantly down-regulated (p<0.01).

Conclusions: For rats with adriamycin-induced nephropathy, irbesartan could significantly reduce proteinuria. As a possible mechanism, irbesartan may improve the slit diaphragm protein of the glomerular podocyte and stabilize the cytoskeleton of the podocyte.

Keywords: Irbesartan; adriamycin-induced nephropathy; nephrin; podocin; podocyte.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Biphenyl Compounds / pharmacology
  • Biphenyl Compounds / therapeutic use*
  • Blood Urea Nitrogen
  • Blotting, Western
  • Body Weight / drug effects
  • Cholesterol / blood
  • Creatinine / blood
  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Desmin / genetics
  • Desmin / metabolism
  • Diaphragm / drug effects
  • Diaphragm / pathology*
  • Doxorubicin / adverse effects*
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Irbesartan
  • Kidney / drug effects
  • Kidney / pathology
  • Kidney / ultrastructure
  • Kidney Diseases / blood
  • Kidney Diseases / chemically induced*
  • Kidney Diseases / drug therapy*
  • Kidney Diseases / urine
  • Male
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Podocytes / drug effects
  • Podocytes / pathology
  • Podocytes / ultrastructure
  • Proteinuria / blood
  • Proteinuria / complications
  • Proteinuria / urine
  • Rats, Wistar
  • Serum Albumin / metabolism
  • Tetrazoles / pharmacology
  • Tetrazoles / therapeutic use*
  • Triglycerides / blood
  • Uric Acid / blood

Substances

  • Adaptor Proteins, Signal Transducing
  • Biphenyl Compounds
  • CD2-associated protein
  • Cytoskeletal Proteins
  • Desmin
  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • NPHS2 protein
  • Serum Albumin
  • Tetrazoles
  • Triglycerides
  • nephrin
  • Uric Acid
  • Doxorubicin
  • Cholesterol
  • Creatinine
  • Irbesartan