AIM: 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. Copyright (c) 2007 S. Karger AG, Basel.
AIM: 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 diabeticrats 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 diabeticrats, 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. Copyright (c) 2007 S. Karger AG, Basel.
Authors: Youli Wang; Kathleen Heilig; Thomas Saunders; Andrew Minto; Dilip K Deb; Anthony Chang; Frank Brosius; Carmela Monteiro; Charles W Heilig Journal: Am J Physiol Renal Physiol Date: 2010-04-07