PMID- 22243699 OWN - NLM STAT- MEDLINE DCOM- 20120813 LR - 20181201 IS - 1440-1797 (Electronic) IS - 1320-5358 (Linking) VI - 17 IP - 4 DP - 2012 May TI - Experimental study of leflunomide on renal protective effect and on inflammatory response of streptozotocin induced diabetic rats. PG - 380-9 LID - 10.1111/j.1440-1797.2012.01563.x [doi] AB - AIM: To further reveal the effects of leflunomide on renal protection and on inflammatory response using streptozotocin (STZ) induced diabetic rats. METHODS: Male Wistar rats were randomly divided into normal control group (NC), diabetic group (DM) and leflunomide treatment group (LEF). LEF group rats were given leflunomide (5 mg/kg) once daily. At the end of the 12th week, general biochemical parameters in three groups were determined. The renal histopathology was observed by light microscopy and electron microscopy. Further biochemical analysis of the gene and protein expression of nuclear factor kappa B (NF-kappaB), tumour necrosis factor-alpha (TNF-alpha), monocyte chemoattractant protein-1 (MCP-1) and ED-1 positive cells in renal tissue were provided using real-time reverse transcription-polymerase chain reaction and immunohistochemistry. RESULTS: Compared with NC group rats, systolic blood pressure, blood glucose (BG), glycohemoglobin (HbAlc), renal hypertrophy index, urine albumin excretion rate (AER) and serum creatinine were increased in DM group rats (P < 0.05). Treatment with leflunomide can improve these parameters except systolic blood pressure, BG and HbAlc. Creatinine clearance rate (Ccr) in the DM group was significantly lower than that of the NC group, and leflunomide can increase its level. Compared with DM group rats, the pathological damages were significantly relieved in LEF group rats. Compared with NC group rats, the gene and protein expressions of NF-kappaB, TNF-alpha, MCP-1 and ED-1 positive cells in renal tissue of DM group rats were highly upregulated (P < 0.01). Leflunomide suppressed their high expressions in renal tissue of diabetic rats. CONCLUSIONS: Leflunomide can ameliorate the kidney structure and function injury of diabetic rats through suppressing the expression of NF-kappaB, TNF-alpha, MCP-1 and macrophage infiltration in renal tissue. CI - (c) 2012 The Authors. Nephrology (c) 2012 Asian Pacific Society of Nephrology. FAU - Yu, Wei-min AU - Yu WM AD - Department of Internal Medicine of Renal Disease, Shanxi Dayi Hospital (Shanxi Academy of Medical Sciences), China. snowfox168408@126.com FAU - Wang, Huan AU - Wang H FAU - Ren, Xiao-Jun AU - Ren XJ FAU - Liu, Jun-Ping AU - Liu JP FAU - Wang, Jian-Ying AU - Wang JY LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Australia TA - Nephrology (Carlton) JT - Nephrology (Carlton, Vic.) JID - 9615568 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Ccl2 protein, rat) RN - 0 (Chemokine CCL2) RN - 0 (Immunosuppressive Agents) RN - 0 (Inflammation Mediators) RN - 0 (Isoxazoles) RN - 0 (NF-kappa B) RN - 0 (Tumor Necrosis Factor-alpha) RN - AYI8EX34EU (Creatinine) RN - G162GK9U4W (Leflunomide) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Biomarkers/blood MH - Chemokine CCL2/genetics/metabolism MH - Creatinine/blood MH - Cytoprotection MH - Diabetes Mellitus, Experimental/complications/*drug therapy/genetics/immunology/metabolism MH - Diabetic Nephropathies/etiology/genetics/immunology/metabolism/*prevention & control MH - Gene Expression Regulation MH - Immunohistochemistry MH - Immunosuppressive Agents/*pharmacology MH - Inflammation/etiology/immunology/metabolism/*prevention & control MH - Inflammation Mediators/metabolism MH - Isoxazoles/*pharmacology MH - Kidney/*drug effects/immunology/metabolism/pathology MH - Leflunomide MH - Male MH - NF-kappa B/genetics/metabolism MH - Nephrectomy MH - Rats MH - Rats, Wistar MH - Real-Time Polymerase Chain Reaction MH - Reverse Transcriptase Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/genetics/metabolism EDAT- 2012/01/17 06:00 MHDA- 2012/08/14 06:00 CRDT- 2012/01/17 06:00 PHST- 2012/01/17 06:00 [entrez] PHST- 2012/01/17 06:00 [pubmed] PHST- 2012/08/14 06:00 [medline] AID - 10.1111/j.1440-1797.2012.01563.x [doi] PST - ppublish SO - Nephrology (Carlton). 2012 May;17(4):380-9. doi: 10.1111/j.1440-1797.2012.01563.x.