Effect of vitamin E and selenium on the tissue inhibitor of metalloproteinase‐1 mRNA expression in hepatic stellate cells

OBJECTIVE: To investigate the effects of vitamin E and different doses of selenium on the expression of the tissue inhibitor of metalloproteinase-1 (TIMP-1) mRNA in the hepatic stellate cells (HSC) of CCl4-induced hepato-fibrotic rats. The mechanism of these therapeutic actions is investigated at a molecular level. METHODS: Hepatic fibroses were induced by intraperitoneal injection of 40% CCl4 in olive oil and treated by dietary supplementation with vitamin E and different doses of selenium. Liver tissue sections were stained with routine hematoxylin and eosin staining and Masson trichrome staining for collagen. With β-actin as an internal control, the reverse transcriptase–polymerase chain reaction (RT-PCR) method was applied to quantify the change of TIMP-1 mRNA in HSC. RESULTS: The expression level of TIMP-1 mRNA in HSC was significantly downregulated and collagenous fiber proliferation in the liver was also significantly reduced in the groups of rats treated with vitamin E (250 mg/kg) and low dosages of selenium (0.2 mg/kg). However, the expression of TIMP-1 mRNA was upregulated, but not significantly, in the group treated with high dosages of selenium (1.0 mg/kg). CONCLUSIONS: The expression level of TIMP-1 mRNA in HSC was significantly downregulated and collagenous fiber proliferation in the liver was significantly reduced in the groups of rats treated with vitamin E and appropriate dosages of selenium. This did not occur in groups with high dosages of selenium.