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

Diwan, Vishal and 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. pp. 104-110. ISSN 1043-6618

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 (10mg/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±2.7mmol/L), PCr (controls: 42±2.8; adenine: 268±23; adenine+glibenclamide: 81±10μmol/L), proteinuria (controls: 150±7.4; adenine: 303±19; adenine+glibenclamide: 220±13μmol/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±14μmol/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.


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Item Type: Article (Commonwealth Reporting Category C)
Refereed: Yes
Item Status: Live Archive
Additional Information: Permanent restricted access to published version due to publisher copyright policy.
Faculty / Department / School: Historic - Faculty of Health, Engineering and Sciences - School of Health, Nursing and Midwifery
Date Deposited: 27 Feb 2015 05:25
Last Modified: 08 Mar 2017 05:16
Uncontrolled Keywords: adenine, glibenclamide, kidney, uric acid
Fields of Research : 06 Biological Sciences > 0606 Physiology > 060699 Physiology not elsewhere classified
11 Medical and Health Sciences > 1115 Pharmacology and Pharmaceutical Sciences > 111599 Pharmacology and Pharmaceutical Sciences not elsewhere classified
Socio-Economic Objective: E Expanding Knowledge > 97 Expanding Knowledge > 970111 Expanding Knowledge in the Medical and Health Sciences
Identification Number or DOI: 10.1016/j.phrs.2013.11.007
URI: http://eprints.usq.edu.au/id/eprint/24648

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