PMID- 15905195
OWN - NLM
STAT- MEDLINE
DCOM- 20051115
LR  - 20171116
IS  - 0931-0509 (Print)
IS  - 0931-0509 (Linking)
VI  - 20
IP  - 8
DP  - 2005 Aug
TI  - Mizoribine reduces renal injury and macrophage infiltration in 
      non-insulin-dependent diabetic rats.
PG  - 1573-81
AB  - BACKGROUND: Macrophage infiltration in kidney is one of the most important events 
      for the progression of diabetic nephropathy. Mycophenolate mofetil (MMF), an 
      anti-inflammatory agent, has been shown to suppress macrophage infiltration and 
      to improve renal injury in streptozotocin-induced diabetic kidneys. We examined 
      whether mizoribine, which acts through immunosuppressive mechanisms similar to 
      MMF, inhibits progression of diabetic nephropathy in non-insulin-dependent 
      diabetic rats. METHODS: Male Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a 
      non-insulin-dependent diabetic model, and Long-Evans Tokushima Otsuka (LETO) 
      rats, a non-diabetic control, were studied at 35 weeks of age. OLETF rats were 
      randomized to receive mizoribine (5 or 10 mg/kg) or normal saline for 8 weeks. 
      Histological changes such as glomerulosclerosis and interstitial fibrosis and the 
      number of ED1- and CD5-positive cells in the kidney were assessed. By using 
      reverse transcription-polymerase chain reaction (RT-PCR) and 
      immunohistochemistry, monocyte chemoattractant protein-1 (MCP-1), osteopontin 
      (OPN) and transforming growth factor (TGF)-beta1 expression in the kidney was 
      also analysed. RESULTS: Urinary albumin excretion in OLETF rats increased 
      compared with that in LETO rats. Administration of mizoribine suppressed urinary 
      albumin excretion. Development of glomerulosclerosis, interstitial fibrosis and 
      macrophage infiltration in the kidney was also inhibited by treatment with 
      mizoribine. The expression of MCP-1, OPN and TGF-beta1 mRNA in untreated OLETF 
      rats was significantly increased compared with that in LETO rats. By 
      immunohistochemistry, increased expression of MCP-1, OPN and TGF-beta1 was found 
      in the tubules and glomeruli of untreated OLETF rats. This expression was 
      significantly suppressed by treatment with mizoribine. CONCLUSIONS: Mizoribine 
      inhibited renal macrophage accumulation and prevented the progression of 
      glomerulosclerosis and interstitial fibrosis in non-insulin-dependent diabetic 
      kidneys. In addition to standard treatments, anti-inflammatory agents may be 
      useful for management of non-insulin-dependent diabetic nephropathy.
FAU - Kikuchi, Yuichi
AU  - Kikuchi Y
AD  - Second Department of Internal Medicine, National Defense Medical College, 3-2 
      Namiki, Tokorozawa, Saitama, 359-8513 Japan. grd1615@ndmc.ac.jp
FAU - Imakiire, Toshihiko
AU  - Imakiire T
FAU - Yamada, Muneharu
AU  - Yamada M
FAU - Saigusa, Takamitsu
AU  - Saigusa T
FAU - Hyodo, Toshitake
AU  - Hyodo T
FAU - Hyodo, Naomi
AU  - Hyodo N
FAU - Suzuki, Shigenobu
AU  - Suzuki S
FAU - Miura, Soichiro
AU  - Miura S
LA  - eng
PT  - Journal Article
DEP - 20050519
PL  - England
TA  - Nephrol Dial Transplant
JT  - Nephrology, dialysis, transplantation : official publication of the European 
      Dialysis and Transplant Association - European Renal Association
JID - 8706402
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Ribonucleosides)
RN  - 0 (Sialoglycoproteins)
RN  - 0 (Spp1 protein, rat)
RN  - 0 (Tgfb1 protein, rat)
RN  - 0 (Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 106441-73-0 (Osteopontin)
RN  - 4JR41A10VP (mizoribine)
RN  - EC 1.1.1.205 (IMP Dehydrogenase)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use
MH  - Chemokine CCL2/genetics/metabolism
MH  - Diabetes Mellitus, Type 2/metabolism
MH  - Diabetic Nephropathies/metabolism/pathology/*prevention & control
MH  - Fibrosis/*drug therapy/pathology
MH  - Glomerulosclerosis, Focal Segmental/*drug therapy/pathology
MH  - IMP Dehydrogenase/antagonists & inhibitors
MH  - Immunoenzyme Techniques
MH  - Macrophages/*drug effects/metabolism/pathology
MH  - Male
MH  - Nephritis, Interstitial/*drug therapy/pathology
MH  - Osteopontin
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Inbred OLETF
MH  - Rats, Long-Evans
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Ribonucleosides/*therapeutic use
MH  - Sialoglycoproteins/genetics/metabolism
MH  - Transforming Growth Factor beta/genetics/metabolism
MH  - Transforming Growth Factor beta1
EDAT- 2005/05/21 09:00
MHDA- 2005/11/16 09:00
CRDT- 2005/05/21 09:00
PHST- 2005/05/21 09:00 [pubmed]
PHST- 2005/11/16 09:00 [medline]
PHST- 2005/05/21 09:00 [entrez]
AID - gfh888 [pii]
AID - 10.1093/ndt/gfh888 [doi]
PST - ppublish
SO  - Nephrol Dial Transplant. 2005 Aug;20(8):1573-81. doi: 10.1093/ndt/gfh888. Epub 
      2005 May 19.