Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats

• Main Author: In Hee Kim1,2, Dae-Ghon Kim1,2*, Peipei Hao2, Yunpeng Wang2, Seong Hun Kim1,2, Sang Wook Kim1,2, Seung Ok Lee1,2 & Soo Teik Lee1,2
• Format: Article
• Language: English
• Published: Korean Society for Biochemistry and Molecular Biology 2012-06-01
• Series: BMB Reports
• Subjects: L-2-Oxothiazolidine-4-carboxylic acid; Liver fibrosis; Nrf2; Oxidative stress; Thioacetamide
• Online Access: http://www.jbmb.or.kr/jbmb/pdf.php?data=MTMwMTIyMTdAcGRmX3JhaW50cmFjZV9sZWV5c0AlNUI0NS02JTVEMTIwNjI2MDcxM18lMjgzNDgtMzUzJTI5Qk1CXzExLTI3Ni5wZGY=

L-2-Oxothiazolidine-4-carboxylic acid (OTC) is a cysteine prodrugthat maintains glutathione in tissues. The present studywas designed to investigate anti-fibrotic and anti-oxidative effectsof OTC via modulation of nuclear factor erythroid 2-relatedfactor 2 (Nrf2) in an in vivo thioacetamide (TAA)-inducedhepatic fibrosis model. Treatment with OTC (80 or 160 mg/kg)improved serum liver function parameters and significantlyameliorated liver fibrosis. The OTC treatment groups exhibitedsignificantly lower expression of α-smooth muscle actin, transforminggrowth factor-β1, and collagen α1 mRNA than that inthe TAA model group. Furthermore, the OTC treatment groupsshowed a significant decrease in hepatic malondialdehyde levelcompared to that in the TAA model group. Nrf2 and hemeoxygenase-1 expression increased significantly in the OTCtreatment 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 liverinjury and a fibrotic reaction.