Rosiglitazone ameliorates diabetic nephropathy by inhibiting reactive oxygen species and its downstream-signaling pathways.
OBJECTIVE
To study whether rosiglitazone prevents the development of diabetic nephropathy through reduction of reactive oxygen species and its downstream signal transduction pathways.


METHODS
The rats were intraperitoneally injected with streptozotocin to induce diabetes, meanwhile the rats in the therapeutic groups were given rosiglitazone (5 or 20 mg/kg/day) for 4 weeks by intragastric administration. Blood glucose, serum lipid and creatinine, urinary albumin excretion were measured. Malondialdehyde content, the activities of nuclear factor-kappaB (NF-kappaB), antioxidant enzymes including Cu-Zn SOD and GSH-Px in kidney were also measured. In addition, the mRNA and protein expression of MCP-1 were semiquantitatively determined with PT-PCR and immunohistochemical staining respectively.


RESULTS
No significant difference of blood glucose and lipid were found between diabetic rats and rosiglitazone treatment groups. The renal histopathology was improved significantly. The expressions of MCP-1 mRNA and protein, malondialdehyde level and the activity of NF-kappaB were decreased markedly in rats treated with high-dose rosiglitazone, but the activities of renal Cu-Zn SOD and GSH-Px increased significantly.


CONCLUSIONS
Rosiglitazone treatment prevented glomerular injury in diabetic rats, which was closely related with its roles of reducing reactive oxygen species, NF-kappaB activation and MCP-1 expression in the early phase of diabetic nephropathy.
Bao
Yan
Y
Division of Nephrology, Renmin Hospital of Wuhan University, Wuhan, PR China.
Jia
Ru-han
RH
Yuan
Jun
J
Li
Jing
J
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors*; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D000097782:NF-kappaB-Inducing Kinase
D007004:Hypoglycemic Agents; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species; D000077154:Rosiglitazone; D045162:Thiazolidinediones; D000097782:NF-kappaB-Inducing Kinase