The Protective Effects of Rosiglitazone on Kidney in Diet-induced Obese Rats

SUN Xiao-dong, YU Ye-rong

Abstract

To investigate whether rosiglitazone has renal protective effects in diet-induced obese rats. Methods?Wistar rats were randomly divided into normal control (NC), obesity (OB) and rosiglitazone (OB+R) group (n=8 in each group). The NC group was fed with normal diet. The OB and OB+R groups were fed with high-fat diet. Four weeks later, rosiglitazone 〔4 mg/(kg·d)〕 was given to the OB+R group by oral gavage. The other two groups were given the same amount of physiological saline in the same manner. After 24 weeks, urinary albumin/creatinine ratio (ACR) was measured. Endothelial function was determined by measuring vasodilatation of aorta. Renal tissues were collected for morphological and CD31 immunohistochemistry. Glomerular vascular endothelial growth factor (VEGF) and nitric oxide （NO) levels were measured. Results?Body weight, visceral fat, plasma free fatty acids (FFAs), plasma triglyceride and ACR levels increased significantly in the obese rats (P<0.01). Rosiglitazone intervention decreased visceral fat, plasma FFAs, plasma triglyceride and ACR levels (P<0.01), which were still higher than NC group (P<0.01). ACR levels of the OB group were higher than those of NC group (P<0.01), while those of OB+R group were lower than those in OB group (P<0.01), but still higher than those of NC group (P<0.05). Endothelium-dependent vasodilatation was impaired in the obese rats. Rosiglitazone intervention could enhance acetylcholine-induced vasorelaxation and improved endothelium-dependent vasodilatation (P<0.05), which was similar to that in NC group (P>0.05). Morphological and immunohistochemistry results showed glomerulomegalia, increased glomerular CD31 expression and increased proliferation of glomerular endothelial cells, which were improved by rosiglitazone (P<0.05). Obese rats showed increased glomerular VEGF and reduced NO levels (P<0.05). This imbalance of VEGF/NO was partly improved by rosiglitazone intervention (P<0.05). Conclusion?Rosiglitazone reduces urinary albumin excretion and has renal protective effects by improving the imbalance of VEGF/NO and endothelial dysfunction in diet-induced obese rats.

 

Keywords: Obesity, Kidney injury, Rosiglitazone 

 

Full Text:

PDF


References


Hu W, Yu Q. Zhang J, et al. Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of Chemerin and ChemR23 in the kidney of streptozotocin-induced diabetic rats. Inflammation,2012;35(4): 1287-1293.

Tang SC, Leung JC, Chan LY, et al. Renoprotection by rosiglitazone in accelerated type 2 diabetic nephropathy: role of STATI inhibition and nephrin restoration. Am J Nephrol, 2010;32(2):145-155.

Arora MK, Reddy K, Balakumar P. The low dose combination of fenofibrate and rosiglitazone halts the progression of diabetes-induced experimental nephropathy. Eur J Pharmacol, 2010;636(1-3):137-144.

Sun X, Yu Y, Han L. High FFA levels related to microalbuminuria and uncoupling of VEGF-ND axis in obese rats. Int Urol Nephrol,2013;45(4): 1197-1207.

Kim EK, Lee JH, Oh YM, et al. Rosiglitazone attenuates hypoxia-induced pulmonary arterial hypertension in rats. Respirology,2010; 15(4) ;659-668.

Sheu WH. Rosiglitazone inhibits endothelial proliferation and angiogenesis. Life Sci,2006; 78(13): 1520-1528.

Petrica L, Petrica M. Vlad A, et aI. Nephro- and neuroprotective effects of rosiglitazone versus glimepiride in normoalbuminuric patients with type 2 diabetes mellitus; a randomized controlled trial. Wien Klin Wochenschr. 2009; 121 (23-24):765-775.

Bahia L. Aguiar LG» Villela N. et al. Effects of rosiglitazone on endothelial function in non-diabetic subjects with metabolic syndrome. Arq Bras Cardiol,2006;86(5):366-373.

Cosson E, Cohen-Boulakia F, Tarhzaoui K, et al. Capillary endothelial but not lymphatic function is restored under rosiglitazone in Zucker diabetic fatty rats. Microvasc Res, 2009;77(2):220-225.

Willems-Widyastuti А, Alagappan VK, Arulmani U, et al. Transforming growth factor-beta 1 induces angiogenesis in vitro via VEGF production in human airway smooth muscle cells. Indian J Biochem Biophys,2011;48(4);262-269.

Lazarus A. Keshet E. Vascular endothelial growth factor and vascular homeostasis. Proc Am Thorac Soc, 2011; 8 ( 6 ); 508- 511.

Wang S, Li Y. Zhao J, et al. Mesenchymal stem cells ameliorate podocyte injury and proteinuria in a type 1 diabetic nephropathy rat model. Biol Blood Marrow Transplant ,2013 ;4 (13):14-21.

Jackson WM. Nesti LJ, Tuan RS. Concise review; clinical translation of wound healing therapies based on mesenchymal stem cells. Stem Cells Transl Med,2012; 1 (1);44-50.

Vojtassak J, Danisovic L, Kubes M, et al. Autologousbiograft and mesenchymal stem cells in treatment of the diabetic foot. Neuro Endocrinol Lett ,2006; 27(2); 134-137.

Hou C, Shen L, Huang Q, et al. The effect of heme oxygenase-1 eomplexed with collagen on MSC performance in the treatment of diabetic ischemic ulcer. Biomaterials, 2013; 34 (1): 112-120.

Hirata Y, Sbimabukuro M, Uematsu E, et al. A synthetic prostacyclin agonist with thromboxane synthase inhibitory activity. ONO-1301, protects myocardium from ischemia/ reperfusion injury. Eur J Pharmacol,2011;674(2-3);353-358.

Kim OJ, Hong SH, Oh SH. Et al. Association between VEGF polymorphisms and homocysteine levels in patients with ischemic stroke and silent brain infarction. Stroke,2011;42(9): 2393-2402.

Brohlin M, Kingham PJ, Novikova LN, et al. Aging effect on neurotrophic activity of human mesenchymal stem cells. PLoS One,2012;7(9) ;e45052.

N Xiong, Z Zhang. J Huang, et al. VEGF-expressing human umbilical cord mesenchymal stem cells, an improved therapy strategy for Parkinson’s disease. Gene Therapy,2011; 18;394- 402.


Refbacks

  • There are currently no refbacks.