title: Experimental study of leflunomide on renal protective effect and on inflammatory response of streptozotocin induced diabetic rats.
abstract: OBJECTIVE
  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-κB), tumour necrosis factor-alpha (TNF-α), 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-κB, TNF-α, 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-κB, TNF-α, MCP-1 and macrophage infiltration in renal tissue.
authors.affiliation: Department of Internal Medicine of Renal Disease, Shanxi Dayi Hospital (Shanxi Academy of Medical Sciences), China. snowfox168408@126.com
authors.forename: Wei-min
authors.initials: WM
authors.lastname: Yu
authors.forename: Huan
authors.initials: H
authors.lastname: Wang
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Ren
authors.forename: Jun-Ping
authors.initials: JP
authors.lastname: Liu
authors.forename: Jian-Ying
authors.initials: JY
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D015415:Biomarkers / Q000097:blood; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D019610:Cytoprotection; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000209:etiology / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007249:Inflammation / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000077339:Leflunomide; D008297:Male; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009392:Nephrectomy; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; C491766:Ccl2 protein, rat; D018932:Chemokine CCL2; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D007555:Isoxazoles; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003404:Creatinine; D000077339:Leflunomide