Pentoxifylline attenuated the renal disease progression in rats with remnant kidney

Shuei Liong Lin, Yung Ming Chen, Chiang Ting Chien, Wen Chih Chiang, Chien Chen Tsai, Tun Jun Tsai

Research output: Contribution to journalArticle

95 Citations (Scopus)

Abstract

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-β1, 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-β1-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.

Original languageEnglish
Pages (from-to)2916-2929
Number of pages14
JournalJournal of the American Society of Nephrology
Volume13
Issue number12
DOIs
Publication statusPublished - 2002 Dec 1

Fingerprint

Pentoxifylline
Disease Progression
Kidney
Kidney Cortex
Cilazapril
Connective Tissue Growth Factor
Transforming Growth Factors
Angiotensin II
Up-Regulation
Fibroblasts
Genes
Mesangial Cells
Phosphodiesterase Inhibitors
Myofibroblasts
Chemokine CCL2
Platelet-Derived Growth Factor
Fibroblast Growth Factor 2
Glomerulonephritis
Nephrectomy
Chronic Renal Insufficiency

ASJC Scopus subject areas

  • Nephrology

Cite this

Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. / Lin, Shuei Liong; Chen, Yung Ming; Chien, Chiang Ting; Chiang, Wen Chih; Tsai, Chien Chen; Tsai, Tun Jun.

In: Journal of the American Society of Nephrology, Vol. 13, No. 12, 01.12.2002, p. 2916-2929.

Research output: Contribution to journalArticle

Lin, Shuei Liong ; Chen, Yung Ming ; Chien, Chiang Ting ; Chiang, Wen Chih ; Tsai, Chien Chen ; Tsai, Tun Jun. / Pentoxifylline attenuated the renal disease progression in rats with remnant kidney. In: Journal of the American Society of Nephrology. 2002 ; Vol. 13, No. 12. pp. 2916-2929.
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