Anti-fibrotic effects of L-2-oxothiazolidine-4-carboxylic acid via modulation of nuclear factor erythroid 2-related factor 2 in rats.
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.
Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju 561-712, Korea.
In Hee
IH
Kim
Dae-Ghon
DG
Kim
Peipei
P
Hao
Yunpeng
Y
Wang
Seong Hun
SH
Kim
Sang Wook
SW
Kim
Seung Ok
SO
Lee
Soo Teik
ST
Lee
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000933:Antifibrinolytic Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008106:Liver Cirrhosis, Experimental / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000737:chemistry / Q000378:metabolism*; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D053778:Thiazolidines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D000199:Actins; D000933:Antifibrinolytic Agents; D024042:Collagen Type I; D051267:NF-E2-Related Factor 2; D053778:Thiazolidines; D053773:Transforming Growth Factor beta1; D008315:Malondialdehyde; D051547:Heme Oxygenase-1; D011761:Pyrrolidonecarboxylic Acid; C029536:2-oxothiazolidine-4-carboxylic acid