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Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy

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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-β1 (TGF-β1), 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-β1, 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.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Grant No. 30873110), by the Key Project of Science and Technology from the Ministry of Education (No. 107133), by the Key Project of the Natural Science Foundation (No. 07-JJ3056) of Hunan Province to Dr. Li-jian Tao. The technical help of Ji-ying Chen, Xuan Zheng, Jiao Qin, Ling Wang, Ling-hao Wang, and Wang-bin Ning is gratefully acknowledged.

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Authors and Affiliations

  1. Division of Nephrology, Department of Internal Medicine, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, China

    Bing-xin Li, Yi-ting Tang, Wei Wang, Yan-yun Xie, Na-sui Wang, Qiong-jing Yuan, Fang-fang Zhang, Zhang-zhe Peng & Li-jian Tao

  2. Faculty of Pharmaceutical Sciences, Central South University, Changsha, 410008, Hunan, China

    Gao-yun Hu

  3. State Key Laboratory of Medical Genetics of China, Central South University, Changsha, 410008, Hunan, China

    Li-jian Tao

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  1. Bing-xin Li
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Correspondence to Li-jian Tao.

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Li, Bx., Tang, Yt., Wang, W. et al. Fluorofenidone attenuates renal interstitial fibrosis in the rat model of obstructive nephropathy. Mol Cell Biochem 354, 263–273 (2011). https://doi.org/10.1007/s11010-011-0826-1

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