Pirfenidone and candesartan ameliorate morphological damage in mild chronic anti-GBM nephritis in rats

Autor: Sabine Leh, Terje Forslund, Øyvind Vaagnes, Solomon B. Margolin, Bjarne M. Iversen
Rok vydání: 2004
Předmět:
Male
medicine.medical_specialty
Combination therapy
Pyridones
Molecular Sequence Data
Tetrazoles
Kidney Function Tests
Sensitivity and Specificity
Antibodies
Drug Administration Schedule
Statistics
Nonparametric
Renal Circulation
Excretion
Random Allocation
Glomerulonephritis
Reference Values
Internal medicine
medicine
Animals
RNA
Messenger
Rats
Wistar
Autoantibodies
Probability
Analysis of Variance
Transplantation
Proteinuria
Base Sequence
Dose-Response Relationship
Drug
Reverse Transcriptase Polymerase Chain Reaction
business.industry
Biopsy
Needle
Biphenyl Compounds
Blood Pressure Determination
Pirfenidone
medicine.disease
Immunohistochemistry
Angiotensin II
Rats
Disease Models
Animal
Candesartan
Blood pressure
Endocrinology
Nephrology
Benzimidazoles
medicine.symptom
business
Blood Chemical Analysis
medicine.drug
Zdroj: Nephrology Dialysis Transplantation. 20:71-82
ISSN: 1460-2385
0931-0509
DOI: 10.1093/ndt/gfh562
Popis: The antifibrotic substance pirfenidone and the angiotensin II type I receptor antagonist candesartan cilexetil, given alone and in combination, were tested in rats with chronic anti-glomerular basement membrane glomerulonephritis (anti-GBM GN).Male Wistar rats with anti-GBM GN were treated for 8 weeks with candesartan (4 mg/kg body weight/day), pirfenidone (500 mg/kg body weight/day) or a combination of both drugs. One GN group received no treatment and untreated non-GN-rats were used as controls. Blood pressure and urinary protein excretion were measured after 3 and 7 weeks. Kidney histology was complemented by ultrastructural investigation and by quantification of collagen Ialpha mRNA.The percentage of glomeruli with adsorption droplets in podocytes correlated well with the amount of proteinuria (r = 0.873, P0.01) and was significantly lowered in rats treated with candesartan (8.3 vs GN 24.6%), pirfenidone (9.8%) and combined treatment (2.6%, P0.05 vs candesartan alone). A comparable lowering was seen for segmental sclerosis (GN 11%, candesartan 0.7%, P0.05 vs GN, pirfenidone 1.8%, P = 0.09 vs GN, candesartan/pirfenidone 0.1%, P0.5 vs candesartan alone). Cortical collagen Ialpha mRNA expression was significantly decreased in all treatment groups. Ultrastructural investigation showed an amelioration of basement membrane alterations and podocyte damage in the treatment groups. Candesartan caused significant blood pressure reduction and the effect was significantly enhanced by combination therapy after 3 weeks. Rats treated with pirfenidone showed blood pressure values similar to control rats.Pirfenidone has a beneficial effect on morphological changes in anti-GBM GN comparable with candesartan although with a trend to slightly better results with candesartan treatment. Moreover, our results suggest an additive effect of combination treatment.
Databáze: OpenAIRE
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