Effect of imidazoline-1 receptor agonists on renal dysfunction in rats associated with chronic, sequential fructose and ethanol administration.

Abstract

Insulin resistance and chronic alcoholism are risk factors for renal dysfunction. This study investigated the therapeutic effects of two imidazoline-1 receptor (I1R) agonists on renal dysfunction in rats after chronic, sequential fructose and ethanol administration. Daily drinking water was supplemented with fructose (10%, w/v) for 12weeks and then with ethanol (20%, v/v) for another 8weeks. Rats were treated with rilmenidine and clonidine in the last two weeks of the study. Blood glucose and serum insulin (sIns) levels, lipid profiles, kidney function and renal histopathology were evaluated at the end of the experiment. Additionally, renal gene expression of nischarin, phosphatidylcholine-specific phospholipase C (PC-PLC) and prostaglandin E2 (PGE2) were measured. Renal levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and total NO (tNO) were detected, and we determined the relative renal gene expression levels of alpha smooth muscle actin (α-SMA), hydroxyproline, interleukin 10 (IL-10), tumour necrosis factor alpha (TNF-α) and caspase-3. The results showed significant deterioration of blood glucose, sIns, lipid profiles, kidney function and renal histopathology in fructose/ethanol-fed rats. Additionally, markers of inflammation, fibrosis, apoptosis and oxidative stress were upregulated. The administration of rilmenidine or clonidine significantly improved blood glucose and sIns levels and reduced renal dysfunction. Our work showed that chronic, sequential fructose and ethanol administration induced fasting hyperglycaemia and renal impairment, and these effects were ameliorated by I1R agonists.