PMID- 10469361
OWN - NLM
STAT- MEDLINE
DCOM- 19991021
LR  - 20171116
IS  - 0085-2538 (Print)
IS  - 0085-2538 (Linking)
VI  - 56
IP  - 3
DP  - 1999 Sep
TI  - Pentoxifylline attenuates experimental mesangial proliferative 
      glomerulonephritis.
PG  - 932-43
AB  - BACKGROUND: Accumulation of glomerular macrophages, proliferation of mesangial 
      cells (MCs), and deposition of extracellular matrix proteins are pathobiological 
      hallmarks of glomerulonephritis. We previously reported that a clinically 
      available nonselective inhibitor of cyclic 3',5'-nucleotide phosphodiesterase, 
      pentoxifylline (PTX), inhibits proliferation of cultured rat MCs, as well as 
      collagen production by these cells. In this study, we investigated the in vivo 
      effects of PTX on rat anti-Thy1 disease, a model of mesangial proliferative 
      nephritis. METHODS: Anti-Thy1 nephritis was induced in Sprague-Dawley rats by 
      injecting mouse anti-rat Thy1 antibodies intravenously. Nephritic rats were 
      randomly assigned to receive PTX (0.1 g/kg/day) or vehicle (phosphate-buffered 
      saline) and were sacrificed at various time points. Paraffin kidney sections were 
      stained with hematoxylin and periodic acid-Schiff reagents for glomerular 
      histology. Frozen kidney sections were stained by monoclonal antibodies against 
      proliferating cell nuclear antigen, ED-1, and alpha-smooth muscle actin and were 
      visualized by color development from a horseradish peroxidase reaction. Monocyte 
      chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), 
      and various extracellular matrix mRNAs were analyzed by Northern blotting. Urine 
      protein concentrations were determined by Lowry's method. RESULTS: Nephritic rats 
      treated with PTX excreted less urinary protein on day 5 of nephritis than 
      vehicle-treated nephritic rats. In periodic acid-Schiff-stained kidneys from 
      PTX-treated nephritic rats, there was attenuation of both glomerular cellularity 
      and glomerular sclerosis compared with vehicle-treated nephritic rats. PTX 
      decreased the augmented glomerular mRNA levels of MCP-1 and ICAM-1 at two hours 
      and on day 1 of nephritis. Immunoreactive staining showed that PTX reduced the 
      number of proliferating glomerular macrophages on days 1, 2, and 3, but not at 
      two hours of nephritis, compared with vehicle-treated nephritic rats. On day 5, 
      PTX decreased the number of activated proliferating MCs and attenuated the 
      glomerular mRNA levels of type I (alpha1), type III (alpha1), and type IV 
      (alpha1) collagen and fibronectin compared with vehicle-treated nephritic rats. 
      CONCLUSION: The administration of PTX to rats with anti-Thy1 disease reduces 
      accumulation and proliferation of glomerular macrophages, attenuates proteinuria, 
      suppresses activation and proliferation of MCs, and ameliorates glomerular 
      sclerosis. These results suggest that PTX may have a suppressive effect in acute 
      phases or relapses of mesangial proliferative glomerulonephritis.
FAU - Chen, Y M
AU  - Chen YM
AD  - Department of Medicine, National Taiwan University Hospital, Taipei, Taiwan.
FAU - Chien, C T
AU  - Chien CT
FAU - Hu-Tsai, M I
AU  - Hu-Tsai MI
FAU - Wu, K D
AU  - Wu KD
FAU - Tsai, C C
AU  - Tsai CC
FAU - Wu, M S
AU  - Wu MS
FAU - Tsai, T J
AU  - Tsai TJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Kidney Int
JT  - Kidney international
JID - 0323470
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokine CCL2)
RN  - 0 (DNA Primers)
RN  - 0 (Fibronectins)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (RNA, Messenger)
RN  - 0 (Thy-1 Antigens)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 9007-34-5 (Collagen)
RN  - SD6QCT3TSU (Pentoxifylline)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/administration & dosage
MH  - Base Sequence
MH  - Cell Division/drug effects
MH  - Chemokine CCL2/genetics
MH  - Collagen/genetics
MH  - DNA Primers/genetics
MH  - Disease Models, Animal
MH  - Fibronectins/genetics
MH  - Glomerular Mesangium/drug effects/pathology
MH  - Glomerulonephritis, Membranoproliferative/*drug therapy/etiology/pathology
MH  - Intercellular Adhesion Molecule-1/genetics
MH  - Macrophages/drug effects/pathology
MH  - Male
MH  - Mice
MH  - Pentoxifylline/*pharmacology
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Proteinuria/drug therapy
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Thy-1 Antigens/immunology
EDAT- 1999/09/01 00:00
MHDA- 1999/09/01 00:01
CRDT- 1999/09/01 00:00
PHST- 1999/09/01 00:00 [pubmed]
PHST- 1999/09/01 00:01 [medline]
PHST- 1999/09/01 00:00 [entrez]
AID - S0085-2538(15)46371-9 [pii]
AID - 10.1046/j.1523-1755.1999.00636.x [doi]
PST - ppublish
SO  - Kidney Int. 1999 Sep;56(3):932-43. doi: 10.1046/j.1523-1755.1999.00636.x.