Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats

Autor: Cira Di Gioia, Raffaella Carletti, Silvia Maestroni, Thomas Unger, Giovanna Castoldi, C. Bombardi, Andrea Stella, Gianpaolo Zerbini, U. Muscha Steckelings, Björn Dahlöf
Přispěvatelé: Castoldi, G, di Gioia, C, Bombardi, C, Maestroni, S, Carletti, R, Muscha Steckelings, U, Dahlöf, B, Unger, T, Zerbini, G, Stella, A, Bedrijfsbureau CD, RS: CARIM - R3 - Vascular biology
Jazyk: angličtina
Rok vydání: 2014
Předmět:
Male
endocrine system diseases
Physiology
Drug Evaluation
Preclinical
experimental models
Blood Pressure
Diabetic nephropathy
urologic and male genital diseases
Kidney
Renal fibrosis
Diabetic Nephropathies
Receptor
Tumor Necrosis Factor-alpha/metabolism
Sulfonamides
diabetic nephropathy
compound 21
urinary albumin excretion
experimental models
renal fibrosis
Zucker diabetic fatty rats
Receptor
Angiotensin
Type 2/agonists
renal fibrosis
Interleukin-10
compound 21
urinary albumin excretion
Albuminuria/drug therapy
Experimental models
Agonist
medicine.medical_specialty
Zucker diabetic fatty rats
Sulfonamides/pharmacology
medicine.drug_class
Diabetes Mellitus
Experimental/complications
Thiophenes/pharmacology
Thiophenes
Compound 21
Receptor
Angiotensin
Type 2
Blood Pressure/drug effects
Losartan
Diabetes Mellitus
Experimental
Interleukin-10/metabolism
Internal medicine
Renin–angiotensin system
medicine
Albuminuria
Animals
Urinary albumin excretion
Diabetic Nephropathies/pathology
business.industry
Tumor Necrosis Factor-alpha
diabetic nephropathy
nutritional and metabolic diseases
Membrane Proteins
medicine.disease
Fibrosis
Rats
Zucker
Kidney/metabolism
Endocrinology
Membrane Proteins/metabolism
business
Zdroj: Castoldi, G, di Gioia, C R, Bombardi, C, Maestroni, S, Carletti, R, Steckelings, U M, Dahlöf, B, Unger, T, Zerbini, G & Stella, A 2014, ' Prevention of diabetic nephropathy by compound 21, selective agonist of angiotensin type 2 receptors, in Zucker diabetic fatty rats ', American Journal of Physiology: Renal Physiology, vol. 307, no. 10, pp. F1123-F1131 . https://doi.org/10.1152/ajprenal.00247.2014
American Journal of Physiology-Renal Physiology, 307(10), F1123-F1131. American Physiological Society
ISSN: 1931-857X
Popis: The aim of this study was to evaluate the effect of compound 21 (C21), a selective AT2 receptor agonist, on diabetic nephropathy and the potential additive effect of C21, when associated with losartan treatment, on the development of albuminuria and renal fibrosis in Zucker diabetic fatty (ZDF) rats. The experiments lasted 15 wk (from 5 to 20 wk of age) and were performed in 40 ZDF rats and 12 control lean rats. ZDF rats were divided into 4 groups: 1) 9 rats were treated with losartan; 2) 10 rats were treated with C21; 3) 9 rats were treated with losartan plus C21; and 4) 12 rats were maintained without any treatment. ZDF rats showed an increase in blood glucose level, albuminuria, renal fibrosis, macrophage infiltration, and TNF-α expression and a reduction of glomerular nephrin expression compared with control lean rats. C21 treatment reduced renal glomerular, tubulointerstitial, and perivascular fibrosis, and macrophage infiltration and TNF-α expression in ZDF rats. C21 treatment caused a decrease in albuminuria in ZDF rats up to 11 wk of age. Losartan decreased macrophage infiltration, TNF-α expression, and renal glomerular and perivascular fibrosis, restored glomerular nephrin expression, but did not affect tubulointerstitial fibrosis. Losartan treatment caused a decrease in albuminuria in ZDF rats up to 15 wk of age. At the end of the protocol, only the combination of C21 plus losartan significantly reduced albuminuria in ZDF rats. These data demonstrate that C21 has beneficial effects on diabetic nephropathy, suggesting the combination of C21 and losartan as a novel pharmacological tool to slow the progression of nephropathy in type II diabetes.
Databáze: OpenAIRE
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