title: Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy.
abstract: Fluorofenidone (FD) is a novel pyridone agent with significant antifibrotic effects in vitro. The purpose of this study is to investigate the effects of FD on renal interstitial fibrosis in rats with obstructive nephropathy caused by unilateral ureteral obstruction (UUO). With pirfenidone (PD, 500 mg/kg/day) and enalapril (10 mg/kg/day) as the positive treatment controls, the rats in different experimental groups were administered with FD (500 mg/kg/day) from day 4 to day 14 after UUO. The tubulointerstitial injury, interstitial collagen deposition, and expression of type I and type III collagen, transforming growth factor-β(1) (TGF-β(1)), connective tissue growth factor (CTGF), platelet-derived growth factor (PDGF), α-smooth muscle actin (α-SMA), and tissue inhibitor of metalloproteinase-1 (TIMP-1) were assessed. FD treatment significantly attenuated the prominently increased scores of tubulointerstitial injury, interstitial collagen deposition, and protein expression of type I and type III collagen in ureter-obstructed kidneys, respectively. As compared with untreated rats, FD also significantly reduced the expression of α-SMA, TGF-β(1), CTGF, PDGF, and inhibitor of TIMP-1 in the obstructed kidneys. Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy through its regulation on fibrogenic growth factors, tubular cell transdifferentiation, and extracellular matrix.
authors: Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, Changsha, 410008 Hunan, China.
authors: Bing-Xin
authors: BX
authors: Li
authors: Yi-Ting
authors: YT
authors: Tang
authors: Wei
authors: W
authors: Wang
authors: Yan-Yun
authors: YY
authors: Xie
authors: Na-Sui
authors: NS
authors: Wang
authors: Qiong-Jing
authors: QJ
authors: Yuan
authors: Fang-Fang
authors: FF
authors: Zhang
authors: Zhang-Zhe
authors: ZZ
authors: Peng
authors: Gao-Yun
authors: GY
authors: Hu
authors: Li-Jian
authors: LJ
authors: Tao
references: J Am Soc Nephrol. 2004 Jun;15(6):1430-40
references: 15153554
references: J Chromatogr B Analyt Technol Biomed Life Sci. 2006 Apr 3;833(2):257-9
references: 16530492
references: J Nephrol. 2001 Nov-Dec;14(6):453-60
references: 11783601
references: Am J Physiol Gastrointest Liver Physiol. 2003 Sep;285(3):G539-46
references: 12791600
references: Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2004 Apr;29(2):139-41
references: 16145895
references: J Am Soc Nephrol. 2002 Jan;13(1):96-107
references: 11752026
references: Am J Physiol Renal Physiol. 2005 Aug;289(2):F227-34
references: 16006588
references: Clin J Am Soc Nephrol. 2007 Sep;2(5):906-13
references: 17702727
references: Am J Physiol Renal Physiol. 2002 Nov;283(5):F861-75
references: 12372761
references: Life Sci. 2008 Jan 16;82(3-4):210-7
references: 18093617
references: Nephrol Dial Transplant. 2007 Dec;22(12):3391-407
references: 17890247
references: J Am Soc Nephrol. 1997 Feb;8(2):199-207
references: 9048338
references: J Am Soc Nephrol. 2005 Sep;16(9):2702-13
references: 15987746
references: Kidney Int. 1994 Apr;45(4):1077-84
references: 8007577
references: Transplantation. 2001 Apr 15;71(7):951-8
references: 11349731
references: Kidney Int. 2000 Oct;58(4):1389-99
references: 11012874
references: J Am Soc Nephrol. 2002 Oct;13(10):2600-10
references: 12239251
references: Kidney Int. 1996 Apr;49(4):1110-9
references: 8691732
references: Anal Biochem. 1999 May 15;270(1):41-9
references: 10328763
references: Kidney Int. 2001 Jul;60(1):96-105
references: 11422741
references: Am J Respir Crit Care Med. 2005 May 1;171(9):1040-7
references: 15665326
references: Kidney Int. 2000 Sep;58(3):1186-201
references: 10972681
references: Ren Fail. 2001 May-Jul;23(3-4):543-9
references: 11499568
references: J Am Soc Nephrol. 2003 Oct;14(10):2544-55
references: 14514732
references: J Am Soc Nephrol. 2007 Jan;18(1):165-75
references: 17135399
references: Dig Liver Dis. 2004 Nov;36(11):744-51
references: 15571005
references: J Am Soc Nephrol. 2009 Aug;20(8):1765-75
references: 19578007
references: Kidney Int. 1997 Sep;52(3):660-73
references: 9291185
references: Nephron Exp Nephrol. 2010;114(3):e83-92
references: 19955828
references: Biochem Pharmacol. 2002 Aug 1;64(3):517-25
references: 12147304
references: Kidney Int. 1998 Jul;54(1):99-109
references: 9648068
references: Am J Physiol Renal Physiol. 2005 May;288(5):F1069-77
references: 15644487
references: J Cell Physiol. 2005 Jun;203(3):599-603
references: 15605366
references: Exp Biol Med (Maywood). 2008 Feb;233(2):109-22
references: 18222966
references: Pharmazie. 2009 Oct;64(10):680-4
references: 19947172
references: Nephrology (Carlton). 2009 Sep;14(6):565-72
references: 19712256
references: Kidney Int. 1995 May;47(5):1285-94
references: 7637258
references: Kidney Int. 1998 Sep;54(3):804-18
references: 9734605