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Title: Anti-oxidant ebselen causes the resolution of experimentally induced hepatic fibrosis in rats
Authors: Wasser, S.
Lim, G.Y.
Ong, C.-N. 
Tan, C.E.L.
Keywords: Cirrhosis
Cytochrome P450
Matrix metalloproteinase-13
Placental form of glutathione-S-transferase
Tissue inhibitor of metalloproteinase-1
Transforming growth factor-β1
Issue Date: 2001
Citation: Wasser, S., Lim, G.Y., Ong, C.-N., Tan, C.E.L. (2001). Anti-oxidant ebselen causes the resolution of experimentally induced hepatic fibrosis in rats. Journal of Gastroenterology and Hepatology (Australia) 16 (11) : 1244-1253. ScholarBank@NUS Repository.
Abstract: Background: Hepatic fibrosis occurs because of injury to the liver parenchyma and biliary system. We have investigated the effect of an organic selenium anti-oxidant, ebselen, in the resolution of experimentally induced hepatic fibrosis, and evaluated its effect on various paradigms involved in hepatic fibrosis. Methods: Following pretreatment with phenobarbitone, liver fibrosis was induced in male Fischer 344 rats by using carbon tetrachloride treatment for 10 weeks. Carbon tetrachloride-treated rats were randomly assigned into two groups: (i) no ebselen; and (ii) ebselen administered for 3 weeks following a 10-week carbon tetrachloride treatment period. Normal controls were: (i) neither carbon tetrachloride nor ebselen treated; or (ii) ebselen treated for 13 weeks. Liver sections were stained with hematoxylin and eosin, Masson trichrome and stained for reticulin by using silver impregnation. Reverse transcription-polymerase chain reaction was used to analyze the steady-state levels of gene(s) involved in: (i) hepatic fibrosis, namely, transforming growth factor-β1, procollagen I and III, tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-13; (ii) oxidative stress, namely, cytochrome P4502E1; and (iii) preneoplastic liver foci, namely, the placental form of glutathione-S-transferase. Results: Histological staining showed that ebselen resolves carbon tetrachloride-induced hepatic fibrosis. Treatment with ebselen reduced steady-state levels of transforming growth factor-β1, procollagen I and III, tissue inhibitor of metalloproteinase-1, cytochrome P4502E1 and placental form glutathione-S-transferase transcripts, and increased transcripts of matrix metalloproteinase-13. Conclusion: These findings provide evidence that ebselen significantly causes the resolution of carbon tetrachloride-induced hepatic fibrosis in rats. © 2001 Blackwell Science Asia Pty Ltd.
Source Title: Journal of Gastroenterology and Hepatology (Australia)
ISSN: 08159319
DOI: 10.1046/j.1440-1746.2001.02621.x
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