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KMID : 0624620120450060348
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BMB Reports
2012 Volume.45 No. 6 p.348 ~ p.353
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Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats
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Kim In-Hee
Kim Dae-Ghon
Hao Peipei
Wang Yunpeng
Kim Seong-Hun
Kim Sang-Wook
Lee Seung-Ok
Lee Soo-Teik
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Abstract
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L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrug that maintains glutathione in tissues. The present study was designed to investigate anti-fibrotic and anti-oxidative effects of OTC via modulation of nuclear factor erythroid 2-related factor 2 (Nrf2) in an in vivo thioacetamide (TAA)-induced hepatic fibrosis model. Treatment with OTC (80 or 160 mg/kg) improved serum liver function parameters and significantly ameliorated liver fibrosis. The OTC treatment groups exhibited significantly lower expression of α-smooth muscle actin, transforming growth factor-β 1, and collagen α 1 mRNA than that in the TAA model group. Furthermore, the OTC treatment groups showed a significant decrease in hepatic malondialdehyde level compared to that in the TAA model group. Nrf2 and heme oxygenase-1 expression increased significantly in the OTC treatment groups compared with that in the TAA model group. Taken together, these results suggest that OTC restores the anti- oxidative system by upregulating Nrf2; thus, ameliorating liver injury and a fibrotic reaction.
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KEYWORD
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L-2-Oxothiazolidine-4-carboxylic acid, Liver fibrosis, Nrf2, Oxidative stress, Thioacetamide
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