Pentoxifylline attenuated the renal disease progression in rats with remnant kidney.
Previous studies have reported that pentoxifylline, a phosphodiesterase inhibitor, attenuates experimental mesangial proliferative glomerulonephritis. This study hypothesized that pentoxifylline could also attenuate the renal disease progression in rats with remnant kidney. After 5/6 subtotal nephrectomy, rats developed progressively elevated proteinuria and plasma creatinine, glomerulosclerosis, interstitial inflammation, and fibrosis, all of which were attenuated by 40 to 60% by pentoxifylline. However, the elevated BP was not changed by pentoxifylline. Pentoxifylline reduced the upregulation of monocyte chemoattractant protein-1 gene by 60% in the cortex of remnant kidney, as well as in a dose-dependent manner in the albumin- or angiotensin II-stimulated proximal tubular cells. It also reduced the upregulation of mitogenic and profibrogenic genes by 50%, including platelet-derived growth factor, fibroblast growth factor-2, transforming growth factor-beta(1), connective tissue growth factor, and types I and III collagen in the cortex of remnant kidney. Furthermore, pentoxifylline was found to decrease the numbers of interstitial myofibroblasts by 60% in the cortex of remnant kidney and suppress the proliferation of cultured interstitial fibroblasts. It also reduced the angiotensin II-induced or transforming growth factor-beta(1)-induced expression of connective tissue growth factor gene in cultured fibroblasts and mesangial cells. Combining pentoxifylline with an angiotensin-converting enzyme inhibitor, cilazapril, almost completely attenuated the renal disease progression in rats with remnant kidney. In conclusion, pentoxifylline alone can attenuate the chronic renal disease progression. Its combination with cilazapril has the potential to prevent the renal disease progression almost completely.
Lin
Shuei-Liong
SL
Department of Internal Medicine, National Taiwan University Hospital, No. 7 Chung-Shan South Road, Taipei, Taiwan.
Chen
Yung-Ming
YM
Chien
Chiang-Ting
CT
Chiang
Wen-Chih
WC
Tsai
Chien-Chen
CC
Tsai
Tun-Jun
TJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D000818:Animals; D001794:Blood Pressure; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics; D017315:Cilazapril / Q000627:therapeutic use; D018450:Disease Progression; D015536:Down-Regulation; D005347:Fibroblasts / Q000473:pathology; D005355:Fibrosis; D015870:Gene Expression / Q000235:genetics; D005920:Glomerular Mesangium / Q000473:pathology; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008938:Mitosis / Q000235:genetics; D009130:Muscle, Smooth / Q000473:pathology; D009392:Nephrectomy / Q000379:methods*; D009393:Nephritis / Q000473:pathology; D010431:Pentoxifylline / Q000627:therapeutic use*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D018932:Chemokine CCL2; D010726:Phosphodiesterase Inhibitors; D017315:Cilazapril; D010431:Pentoxifylline