Abstract
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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / genetics
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Actins / metabolism
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Animals
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Antifibrinolytic Agents / chemistry
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Antifibrinolytic Agents / pharmacology*
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Antifibrinolytic Agents / therapeutic use
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Collagen Type I / genetics
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Collagen Type I / metabolism
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Gene Expression Regulation / drug effects*
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Heme Oxygenase-1 / metabolism
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Liver Cirrhosis, Experimental / drug therapy
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Liver Cirrhosis, Experimental / metabolism
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Liver Cirrhosis, Experimental / pathology
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Male
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Malondialdehyde / metabolism
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NF-E2-Related Factor 2 / chemistry
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NF-E2-Related Factor 2 / metabolism*
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Pyrrolidonecarboxylic Acid / chemistry
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Pyrrolidonecarboxylic Acid / pharmacology*
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Pyrrolidonecarboxylic Acid / therapeutic use
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Rats
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Rats, Sprague-Dawley
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Thiazolidines / chemistry
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Thiazolidines / pharmacology*
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Thiazolidines / therapeutic use
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Transforming Growth Factor beta1 / genetics
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Transforming Growth Factor beta1 / metabolism
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Up-Regulation / drug effects
Substances
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Actins
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Antifibrinolytic Agents
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Collagen Type I
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NF-E2-Related Factor 2
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Thiazolidines
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Transforming Growth Factor beta1
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Malondialdehyde
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Heme Oxygenase-1
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Pyrrolidonecarboxylic Acid
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2-oxothiazolidine-4-carboxylic acid