Anti-oxidant ebselen causes the resolution of experimentally induced hepatic fibrosis in rats
| Autor: | Shanthi Wasser, Carolyn Eng Looi Tan, Choon Nam Ong, Ganymede Y Lim |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Azoles
Male medicine.medical_specialty Cirrhosis H&E stain Isoindoles Liver Cirrhosis Experimental medicine.disease_cause Antioxidants Masson's trichrome stain chemistry.chemical_compound Fibrosis Organoselenium Compounds Internal medicine medicine Animals Glutathione Transferase Hepatology Ebselen business.industry Remission Induction Gastroenterology Metalloendopeptidases Cytochrome P-450 CYP2E1 medicine.disease Rats Inbred F344 Rats Endocrinology chemistry Transforming Growth Factors Carbon tetrachloride Hepatic fibrosis business Procollagen Oxidative stress |
| Zdroj: | Journal of Gastroenterology and Hepatology. 16:1244-1253 |
| ISSN: | 1440-1746 0815-9319 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text