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

研究成果: 雜誌貢獻文章同行評審

100 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)2916-2929
頁數14
期刊Journal of the American Society of Nephrology
13
發行號12
DOIs
出版狀態已發佈 - 2002 十二月

ASJC Scopus subject areas

  • Nephrology

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