KMID : 0360220140550071077
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Journal of the Korean Ophthalmological Society 2014 Volume.55 No. 7 p.1077 ~ p.1083
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Cytotoxicities and Anti-Fibrotic Effects of Pirfenidone and Mitomycin C on Human Fibroblasts
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Park Kyoung-Soo
Hong Sa-Min Iizuka Yoko Kim Chan-Yun Seong Gong-Je
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Abstract
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Purpose: The cytotoxicities and anti-fibrotic effects of mitomycin C and pirfenidone on human dermal fibroblast were evaluated.
Methods: Initially, 24-hour cell cultures were exposed to transforming growth factor (TGF)-¥â1, different concentrations of mitomycin C, and pirfenidone solutions in order to evaluate cytotoxicity. Expressions of fibronectin, collagen type 1, ¥á smooth muscle, and ¥â-actin were evaluated by real-time reverse transcription-polymerase chain reaction (RT-PCR) and western blot in mitomycin C solutions at concentrations of 4 ¥ìg/mL and 20 ¥ìg/mL, and in pirfenidone solutions at 250 ¥ìg/mL and 500 ¥ìg/mL.
Results: In comparison to cell cultures exposed to TGF-¥â1 solutions, cytotoxicities were increased in solutions of mitomycin C at 4 ¥ìg/mL, 20 ¥ìg/mL, 40 ¥ìg/mL and pirfenidone at 500 ¥ìg/mL, 750 ¥ìg/mL, 1,000 ¥ìg/mL (p < 0.05, Mann Whitney U-test). The results of real-time RT-PCR show that expressions of fibronectin, collagen type 1, and ¥á smooth muscle were significantly more decreased in all concentrations of mitomycin C and pirfenidone compared to those in TGF-¥â1 solution. In western blot analysis, expressions of fibronectin and ¥á smooth muscle were decreased in all concentrations of mitomycin C and pirfenidone compared to TGF-¥â1 solution.
Conclusions: Both drugs have cytotoxicities and anti-fibrotic effects, but pirfenidone was found to have less cytotoxicity and mitomycin C was found to have more anti-fibrotic effects when compared to each other.
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KEYWORD
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Anti-fibrotic effect, Cytotoxicity, Mitomycin C, Pirfenidone
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