PMID- 16428080
OWN - NLM
STAT- MEDLINE
DCOM- 20090223
LR  - 20161124
IS  - 1567-5769 (Print)
IS  - 1567-5769 (Linking)
VI  - 6
IP  - 3
DP  - 2006 Mar
TI  - Prevention of early renal injury by mycophenolate mofetil and its mechanism in 
      experimental diabetes.
PG  - 445-53
AB  - Previously it was shown that treatment with mycophenolate mofetil (MMF) 
      attenuated renal inflammation and glomerular injury in a model of diabetes. 
      However, the mechanism involved in the renoprotective effects of MMF in 
      experimental diabetes has not been clearly delineated. Diabetes was induced by 
      injection of streptozotocin (STZ) after uninephrectomy. Diabetic animals received 
      no treatment or treatment with MMF (10 mg/kg once daily by gastric gavage) for 8 
      weeks, non-diabetic rats served as controls. Level of malondialdehyde (MDA) in 
      renal tissue and urine as well as the activity of antioxidant enzymes (AOE) in 
      renal tissue was determined. Renal injury was evaluated. Immunohistochemistry for 
      ED-1 macrophages marker, intercellular adhesion molecule-1 (ICAM-1) and monocyte 
      chemoattractant protein-1 (MCP-1) was performed. Expression of transforming 
      growth factor (TGF)-beta1 protein was determined by Western blotting analysis. 
      Treatment with MMF had no effect on blood glucose level, but did prevent 
      increased urinary albumin excretion and glomerular damage in diabetic rats. 
      Oxidative stress was reduced by MMF treatment, as indicated by a reduction in MDA 
      level in renal tissue and urine. Activity of AOE such as glutathione peroxidase 
      (GSH-PX) was markedly elevated while superoxide dismutase (SOD) and catalase 
      (CAT) were not changed by MMF treatment. In diabetic animals receiving no 
      treatment, there were increases in ED-1-positive cells, ICAM-1 expression and 
      MCP-1 expression in glomeruli and tubulointerstitium, which were effectively 
      suppressed by MMF treatment. Western blotting analysis showed that the expression 
      of TGF-beta1 protein was increased by 1.92-fold in renal tissue in diabetic rats, 
      and MMF treatment significantly reduced the increased expression of TGF-beta1 
      protein by 45%. Our data suggest that MMF treatment ameliorates early renal 
      injury via the inhibition of oxidative stress and overexpression of ICAM-1, MCP-1 
      and TGF-beta1 in renal tissue in diabetic rats.
FAU - Wu, Yong-Gui
AU  - Wu YG
AD  - Department of Nephropathy, the First Affiliated Hospital of Anhui Medical 
      University, Hefei, Anhui, People's Republic of China. wygxll@ah163.com
FAU - Lin, Hui
AU  - Lin H
FAU - Qi, Xiang-Ming
AU  - Qi XM
FAU - Wu, Guo-Zhong
AU  - Wu GZ
FAU - Qian, Hao
AU  - Qian H
FAU - Zhao, Min
AU  - Zhao M
FAU - Shen, Ji-Jia
AU  - Shen JJ
FAU - Lin, Shan-Tan
AU  - Lin ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20051012
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Chemokine CCL2/biosynthesis/genetics
MH  - Diabetes Mellitus, Experimental/complications/*drug therapy
MH  - Diabetic Nephropathies/metabolism/pathology/*prevention & control
MH  - Intercellular Adhesion Molecule-1/biosynthesis/genetics
MH  - Kidney/cytology/*drug effects/metabolism/pathology
MH  - Macrophages/cytology/pathology
MH  - Male
MH  - Mycophenolic Acid/*analogs & derivatives/pharmacology
MH  - Oxidative Stress/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Transforming Growth Factor beta1/biosynthesis/genetics
EDAT- 2006/01/24 09:00
MHDA- 2009/02/24 09:00
CRDT- 2006/01/24 09:00
PHST- 2005/04/03 00:00 [received]
PHST- 2005/06/30 00:00 [revised]
PHST- 2005/09/15 00:00 [accepted]
PHST- 2006/01/24 09:00 [pubmed]
PHST- 2009/02/24 09:00 [medline]
PHST- 2006/01/24 09:00 [entrez]
AID - S1567-5769(05)00261-4 [pii]
AID - 10.1016/j.intimp.2005.09.006 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2006 Mar;6(3):445-53. doi: 10.1016/j.intimp.2005.09.006. 
      Epub 2005 Oct 12.