PMID- 24855017
OWN - NLM
STAT- MEDLINE
DCOM- 20150219
LR  - 20220321
IS  - 1660-2129 (Electronic)
IS  - 1660-2129 (Linking)
VI  - 126
IP  - 3
DP  - 2014
TI  - Synergistic effects of leflunomide and benazepril in streptozotocin-induced 
      diabetic nephropathy.
PG  - 148-56
LID - 10.1159/000362556 [doi]
AB  - BACKGROUND: Leflunomide (LEF) and benazepril have renoprotective effects on 
      diabetic nephropathy (DN) through their anti-inflammatory and anti-fibrotic 
      activities. This study investigated whether combined treatment using LEF and 
      benazepril affords superior protection compared with the respective 
      monotherapies. METHODS: Diabetes was induced with streptozotocin (STZ, 65 mg/kg) 
      by intraperitoneal injection in male Wistar rats. Two weeks after STZ injection, 
      diabetic rats were treated daily for 12 weeks with LEF (10 mg/kg), benazepril (10 
      mg/kg), or a combination of both. Basic parameters (body weight, fasting blood 
      glucose level, and 24 h urinary protein excretion), histopathology, inflammatory 
      [inflammatory cell infiltration (ED-1), monocyte chemoattractant protein-1 
      (MCP-1), and Toll-like receptor-2 (TLR-2)] and glomerulosclerotic factors 
      [transforming growth factor-beta1 (TGF-beta1) and connective tissue growth factor 
      (CTGF)], and oxidative stress (8-hydroxy-2'-deoxyguanosine, 8-OHdG) were studied. 
      RESULTS: Benazepril or LEF treatment significantly prevented body weight loss and 
      24 h urinary protein excretion induced by diabetes; combined treatment with LEF 
      and benazepril further improved these parameters compared with giving each drug 
      alone (all p < 0.01). Increased expression of inflammatory (MCP-1 and TLR-2) and 
      glomerulosclerotic (TGF-beta1 and CTGF) factors in diabetic rat kidney was reduced 
      by treatment with either LEF or benazepril and was further reduced by the 
      combined administration of the two drugs (p < 0.01). These effects were 
      accompanied by suppression of urinary 8-OHdG excretion. There was no significant 
      between-group difference in blood glucose level. CONCLUSIONS: LEF treatment 
      lessens DN, and combined treatment with LEF and benazepril provides synergistic 
      effects in preventing DN.
CI  - 2014 S. Karger AG, Basel
FAU - Jin, Hua
AU  - Jin H
AD  - Nephrology and Dialysis Unit, Department of Internal Medicine, Yanbian University 
      Hospital, Yanji, Jilin Province, PR China.
FAU - Piao, Shang Guo
AU  - Piao SG
FAU - Jin, Ji Zhe
AU  - Jin JZ
FAU - Jin, Ying Shun
AU  - Jin YS
FAU - Cui, Zhen Hua
AU  - Cui ZH
FAU - Jin, Hai Feng
AU  - Jin HF
FAU - Zheng, Hai Lan
AU  - Zheng HL
FAU - Li, Jin Ji
AU  - Li JJ
FAU - Jiang, Yu Ji
AU  - Jiang YJ
FAU - Yang, Chul Woo
AU  - Yang CW
FAU - Li, Can
AU  - Li C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140516
PL  - Switzerland
TA  - Nephron Exp Nephrol
JT  - Nephron. Experimental nephrology
JID - 101159770
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antifibrinolytic Agents)
RN  - 0 (Benzazepines)
RN  - 0 (Isoxazoles)
RN  - G162GK9U4W (Leflunomide)
RN  - UDM7Q7QWP8 (benazepril)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/administration & dosage
MH  - Antifibrinolytic Agents/administration & dosage
MH  - Benzazepines/*administration & dosage
MH  - Diabetes Mellitus, Experimental/*drug therapy/pathology
MH  - Diabetic Nephropathies/*drug therapy/pathology
MH  - Drug Synergism
MH  - Isoxazoles/*administration & dosage
MH  - Leflunomide
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Treatment Outcome
EDAT- 2014/05/24 06:00
MHDA- 2015/02/20 06:00
CRDT- 2014/05/24 06:00
PHST- 2013/10/24 00:00 [received]
PHST- 2014/03/25 00:00 [accepted]
PHST- 2014/05/24 06:00 [entrez]
PHST- 2014/05/24 06:00 [pubmed]
PHST- 2015/02/20 06:00 [medline]
AID - 000362556 [pii]
AID - 10.1159/000362556 [doi]
PST - ppublish
SO  - Nephron Exp Nephrol. 2014;126(3):148-56. doi: 10.1159/000362556. Epub 2014 May 
      16.