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 12 weeks and then with ethanol (20%, v/v) for another 8 weeks. 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.

Pioglitazone Enhances β-Arrestin2 Signaling and Ameliorates Insulin Resistance in Classical Insulin Target Tissues

“…We showed previously and in the current study that feeding Swiss albino mice with HFrHFD for 16 weeks induces an early stage of IR characterized by slightly reduced or normal body weight, normo- or slight hyperglycemia, and profound hyperinsulinemia [13, 14]. Both fructose and saturated fats used in this type of diet contribute to the IR state by promoting the degradation of the IRS-1 and downregulation of the insulin receptors [21, 22]. In addition, saturated fats through their effect on FFAR1 can mediate hyperinsulinemia, the main characteristic feature of this model [23].…”

<p>Emodin Retarded Renal Fibrosis Through Regulating HGF and TGFβ–Smad Signaling Pathway</p>

“…3 Furthermore, it has been confirmed that chronic kidney disease patients account for 10% of the world's total population. 4,5 As such, a new method for cure of renal fibrosis is of great significance. HGF) contains an α-chain and a β-chain.…”