Rosiglitazone alleviates injury in rats with adenine-induced chronic kidney disease

Abstract

Abstract. Rosiglitazone (ROG) has been shown to exert beneficial effects on glycemic control and renal protection. Circulatory fibroblast growth factor-23 (FGF-23) is a novel independent risk factor for chronic kidney disease (CKD) progression. The current study focused on how ROG impacts on injury of the kidney, and whether FGF-23 is involved in the process. A total of 24 male Sprague Dawley rats, weighing 250-280 g, were divided into four groups (n=6 per group): i) Normal; ii) ROG controls, treated with ROG (10 mg/kg/day); iii) CKD models, treated with adenine (200 mg/kg/day); and iv) ROG treatment, treated with ROG (10 mg/kg/day) and adenine (200 mg/kg/day). The rats were sacrificed after four weeks, and serum, urine and kidney tissues were collected. The data revealed that the serum levels of inorganic phosphate (Pi), intact parathyroid hormone (iPTH) and FGF-23 were significantly higher in the CKD models compared with those in the normal group (P<0.01), while ROG significantly reduced the serum levels of Pi, iPTH and FGF-23 (P<0.01). The ratio of protein/creatine (Cr) in the urine and the serum levels of Cr, blood urea nitrogen and uric acid were significantly increased in the CKD models compared with the normal group (P<0.01), however, ROG significantly reduced these parameters (P<0.05). Furthermore, ROG significantly alleviated the tubule interstitial damage index of the CKD models in comparison with that of the controls. These results indicated that ROG mitigates the lesions of chronic kidney disease induced by adenine, and that the system of Pi-PTH-FGF-23 may contribute to this process. The possible mechanisms underlying this process require confirmation in future studies.

Neurological sequel of chronic kidney disease: From diminished Acetylcholinesterase activity to mitochondrial dysfunctions, oxidative stress and inflammation in mice brain

“…These findings are consistent with others 49–62 and our previous work 23 . In addition, the adenine-induced CKD in rodent models have been reported to cause cardiovascular damages 58 , including increase in left ventricular fibrosis, ventricular stiffness, and wall thickness 56 , increased blood pressure 56,62 , oxidative stress and inflammation including elevation in the activities of SOD, leukocyte infiltration, increased expression of NF-κB 60 , heme oxygenase-1, TNF-α and NOD-like receptor protein-3 56,60 , elevated levels of parathyroid hormone 60,63 , phosphate 56,60 , and anaemia with decrease in erythrocyte count, hematocrit, haemoglobin and erythropoietin 59 , and decrease in food intake 60 , similar to human subjects. This makes the adenine model to be a valid and highly reproducible model, and thereby justifies the use of the model for the present study.…”

Pioglitazone Improves Mitochondrial Function in the Remnant Kidney and Protects against Renal Fibrosis in 5/6 Nephrectomized Rats

“…As a kind of effective antidiabetic drug, PPARγ agonists not only conquer diabetic nephropathy, but they are also considered potential therapeutic agents in non-diabetic CKD ( Fogo, 2011 ). Previous studies have demonstrated that rosiglitazone could protect kidney from damage induced by several factors ( Huang et al, 2013 ; Kumar et al, 2013 ; Korolczuk et al, 2014 ). Pioglitazone attenuated renal ischemia-reperfusion injury through its anti-inflammatory and antioxidant effects ( Reel et al, 2013 ; Zou et al, 2013 ), reduced kidney damage in diabetic rats through increasing glomerular podocalyxin protein expression ( Peng et al, 2014 ) and provided renoprotection by interfering with the renin-angiotensin system and profibrotic proteins ( Ochodnicky et al, 2014 ).…”

Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations

“…Eighty adult male Sprague Dawley rats 220 ± 20 gm and 6–8 weeks old were obtained from the animal house faculty of veterinary medicine, Zagazig University and were maintained under standard conditions for experimentation on rodents. Nephropathy was induced in rats via the administration of adenine (Sigma–Aldrich Chemical Co., St. Louis, MO, USA) 200 mg/kg body weight (b.wt) in 0.5% carboxymethyl cellulose (CMC) (Sigma–Aldrich Chemical Co., St. Louis, MO, USA) daily for 24 consecutive days [ 32 ].…”