Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease

Diwan, Vishal, Gobe, Glenda and Brown, Lindsay (2014) Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease. Pharmacological Research, 79 104-110. doi:10.1016/j.phrs.2013.11.007


Author Diwan, Vishal
Gobe, Glenda
Brown, Lindsay
Title Glibenclamide improves kidney and heart structure and function in the adenine-diet model of chronic kidney disease
Journal name Pharmacological Research   Check publisher's open access policy
ISSN 1043-6618
1096-1186
Publication date 2014-01-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.phrs.2013.11.007
Open Access Status Not Open Access
Volume 79
Start page 104
End page 110
Total pages 7
Place of publication London, United Kingdom
Publisher Academic Press
Language eng
Formatted abstract
The development of chronic kidney disease (CKD) and associated cardiovascular disease involves free radical damage and inflammation. Addition of adenine to the diet induces inflammation followed by CKD and cardiovascular disease. NOD-like receptor protein-3 (NLRP-3) is pro-inflammatory in the kidney; glibenclamide inhibits production of NLRP-3. Male Wistar rats were fed either control rat food or adenine (0.25%) in this food for 16 weeks. Glibenclamide (10 mg/kg/day) was administered to two groups with and without adenine for the final 8 weeks. Kidney function (blood urea nitrogen/BUN, plasma creatinine/PCr, plasma uric acid, proteinuria), kidney structure (fibrosis, inflammation), cardiovascular parameters (blood pressure, left ventricular stiffness, vascular responses and echocardiography) and protein expression of markers for oxidative stress (HO-1), and inflammation (TNF-α, NLRP-3) were assessed. In adenine-fed rats, glibenclamide decreased BUN (controls: 6 ± 0.6; adenine: 56.6 ± 5.4; adenine + glibenclamide: 19.4 ± 2.7 mmol/L), PCr (controls: 42 ± 2.8; adenine: 268 ± 23; adenine + glibenclamide: 81 ± 10 μmol/L), proteinuria (controls: 150 ± 7.4; adenine: 303 ± 19; adenine + glibenclamide: 220 ± 13 μmol/L) (all p < 0.05). Glibenclamide decreased infiltration of chronic inflammatory cells, fibrosis, tubular damage and expression of HO-1, TNF-α and NLRP-3 in the kidney. Glibenclamide did not alter plasma uric acid concentrations (controls: 38 ± 1; adenine: 63 ± 4; adenine + glibenclamide: 69 ± 14 μmol/L). Cardiovascular changes included decreased systolic blood pressure and improved vascular responses although cardiac fibrosis, left ventricular stiffness and hypertrophy were not reduced. Glibenclamide improved kidney structure and function in CKD and decreased some cardiovascular parameters. Inflammatory markers and cell populations were attenuated by glibenclamide in kidneys.
Keyword Adenine
Glibenclamide
Kidney
Uric acid
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
School of Biomedical Sciences Publications
School of Medicine Publications
 
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