Phosphodiesterase Inhibitor Improves Renal Tubulointerstitial Hypoxia of the Diabetic Rat Kidney
The Korean Journal of Internal Medicine
; : 163-170, 2012.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-28115
Responsible library:
WPRO
ABSTRACT
BACKGROUND/AIMS:
Renal hypoxia is involved in the pathogenesis of diabetic nephropathy. Pentoxifyllin (PTX), a nonselective phosphodiesterase inhibitor, is used to attenuate peripheral vascular diseases. To determine whether PTX can improve renal hypoxia, we investigated its effect in the streptozocin (STZ)-induced diabetic kidney.METHODS:
PTX (40 mg/kg, PO) was administered to STZ-induced diabetic rats for 8 weeks. To determine tissue hypoxia, we examined hypoxic inducible factor-1alpha (HIF-1alpha), heme oxygenase-1 (HO-1), vascular endothelial growth factor (VEGF), and glucose transporter-1 (GLUT-1) levels. We also tested the effect of PTX on HIF-1alpha in renal tubule cells.RESULTS:
PTX reduced the increased protein creatinine ratio in diabetic rats at 8 weeks. HIF-1alpha, VEGF, and GLUT-1 mRNA expression increased significantly, and the expression of HO-1 also tended to increase in diabetic rats. PTX significantly decreased mRNA expression of HIF-1alpha and VEGF at 4 and 8 weeks, and decreased HO-1 and GLUT-1 at 4 weeks. The expression of HIF-1alpha protein was significantly increased at 4 and 8 weeks in tubules in the diabetic rat kidney. PTX tended to decrease HIF-1alpha protein expression at 8 weeks. To examine whether PTX had a direct effect on renal tubules, normal rat kidney cells were stimulated with CoCl2 (100 microM), which enhanced HIF-1alpha mRNA and protein levels under low glucose conditions (5.5 mM). Their expressions were similar even after high glucose (30 mM) treatment. PTX had no effect on HIF-1alpha expression.CONCLUSIONS:
PTX attenuates tubular hypoxia in the diabetic kidney.
Full text:
Available
Database:
WPRIM (Western Pacific)
Main subject:
Pentoxifylline
/
Phosphodiesterase Inhibitors
/
Time Factors
/
RNA, Messenger
/
Cell Line
/
Gene Expression Regulation
/
Rats, Sprague-Dawley
/
Cobalt
/
Streptozocin
/
Vascular Endothelial Growth Factor A
Type of study:
Prognostic study
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Internal Medicine
Year:
2012
Document type:
Article