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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

  • Kim, In-Hee (Department of Internal Medicine, Chonbuk National University Medical School and Hospital) ;
  • Kim, Dae-Ghon (Department of Internal Medicine, Chonbuk National University Medical School and Hospital) ;
  • Hao, Peipei (Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital) ;
  • Wang, Yunpeng (Research Institute of Clinical Medicine, Chonbuk National University Medical School and Hospital) ;
  • Kim, Seong-Hun (Department of Internal Medicine, Chonbuk National University Medical School and Hospital) ;
  • Kim, Sang-Wook (Department of Internal Medicine, Chonbuk National University Medical School and Hospital) ;
  • Lee, Seung-Ok (Department of Internal Medicine, Chonbuk National University Medical School and Hospital) ;
  • Lee, Soo-Teik (Department of Internal Medicine, Chonbuk National University Medical School and Hospital)
  • Received : 2011.12.22
  • Accepted : 2012.03.12
  • Published : 2012.06.30

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 ${\alpha}$-smooth muscle actin, transforming growth factor-${\beta}1$, and collagen ${\alpha}1$ 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.

Keywords

References

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