PMID- 16830106
OWN - NLM
STAT- MEDLINE
DCOM- 20061026
LR  - 20161124
IS  - 1023-3830 (Print)
IS  - 1023-3830 (Linking)
VI  - 55
IP  - 5
DP  - 2006 May
TI  - Renoprotective effects of combination of angiotensin converting enzyme inhibitor 
      with mycophenolate mofetil in diabetic rats.
PG  - 192-9
AB  - OBJECTIVE AND DESIGN: Previously it was shown that blocking of the 
      renin-angiotensin system (RAS) by angiotensin converting enzyme (ACE) inhibitors, 
      or suppression of inflammatory responses by immunosuppressive drugs such as 
      mycophenolate mofetil (MMF) could attenuate renal injury in diabetic rats. 
      Whether RAS blockade combined with an immunosuppressive drug provides superior 
      renoprotection against diabetic nephropathy has not been clearly delineated. 
      MATERIALS: Diabetes was induced by injection of streptozotocin after 
      uninephrectomy. TREATMENT: Rats were randomly separated into five groups: 
      control, diabetes, diabetes treated with enalapril (an ACE inhibitor, 10 mg/kg/d 
      by gastric gavage), diabetes treated with MMF (10 mg/kg/d by gastric gavage), or 
      diabetes treated with a combination of both agents and were followed for 8 weeks. 
      METHODS: 24 h urinary albumin excretion rate (AER) was determined, renal injury 
      was evaluated, immunohistochemistry for ED-1 macrophage marker, intercellular 
      adhesion molecule-1 (ICAM-1) and monocyte chemoattractant protein-1 (MCP-1) were 
      performed, and expression of transforming growth factor (TGF)-beta1 protein was 
      determined by Western blotting analysis. RESULTS: Diabetes was associated with a 
      considerable increase in AER. Both enalapril and MMF retarded the increase in 
      albuminuria, which was nearly completely abrogated by combination therapy. 
      Increased glomerular volume and tubulointerstitial injury index in diabetic rats 
      was attenuated by treatment with either enalapril or MMF and further reduced by 
      the combination of the two. Elevated malondialdehyde levels in renal tissue were 
      reduced by enalapril or MMF and, more effectively, by combined enalapril with 
      MMF. Renal overexpression of ICAM-1 was not retarded by enalapril and attenuated 
      by MMF or combined enalapril with MMF. Combination therapy was associated with a 
      superior suppression of diabetes-induced macrophage recruitment and 
      overexpression of MCP-1 and TGFbeta1 compared to either monotherapy in renal 
      tissue. CONCLUSION: The combination of enalapril and MMF confers superiority over 
      monotherapy in renoprotection, a mechanism which may be at least partly 
      correlated with synergistic suppression of increased macrophage recruitment and 
      overexpression of MCP-1 and TGF-beta1 in renal tissue in diabetic rats.
FAU - Wu, Y-G
AU  - Wu YG
AD  - Department of Nephropathy, the First Affiliated Hospital of AnHui Medical 
      University, 230022, Hefei, China. wygxll@ah163.com
FAU - Lin, H
AU  - Lin H
FAU - Qian, H
AU  - Qian H
FAU - Zhao, M
AU  - Zhao M
FAU - Qi, X-M
AU  - Qi XM
FAU - Wu, G-Z
AU  - Wu GZ
FAU - Lin, S-T
AU  - Lin ST
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Inflamm Res
JT  - Inflammation research : official journal of the European Histamine Research 
      Society ... [et al.]
JID - 9508160
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Ccl2 protein, rat)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 4Y8F71G49Q (Malondialdehyde)
RN  - 69PN84IO1A (Enalapril)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Albuminuria/drug therapy
MH  - Angiotensin-Converting Enzyme Inhibitors/*pharmacology
MH  - Animals
MH  - Chemokine CCL2/metabolism
MH  - Diabetes Mellitus, Experimental/*drug therapy/immunology/metabolism
MH  - Drug Therapy, Combination
MH  - Enalapril/*pharmacology
MH  - Immunosuppressive Agents/*pharmacology
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - Kidney/drug effects/metabolism/pathology
MH  - Macrophages/drug effects/immunology
MH  - Male
MH  - Malondialdehyde/metabolism
MH  - Mycophenolic Acid/*analogs & derivatives/pharmacology
MH  - Oxidative Stress/drug effects
MH  - Rats
MH  - Rats, Wistar
MH  - Transforming Growth Factor beta/metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2006/07/11 09:00
MHDA- 2006/10/27 09:00
CRDT- 2006/07/11 09:00
PHST- 2006/07/11 09:00 [pubmed]
PHST- 2006/10/27 09:00 [medline]
PHST- 2006/07/11 09:00 [entrez]
AID - 10.1007/s00011-006-0070-4 [doi]
PST - ppublish
SO  - Inflamm Res. 2006 May;55(5):192-9. doi: 10.1007/s00011-006-0070-4.