Combination of Selenium and Vitamin E Inhibits Type I Collagen Formation in Cultured Hepatic Stellate Cells

• Published in: Biological trace element research 2011-04, Vol.140 (1), p.82-94
• Main Authors: Mezey, Esteban, Liu, Xiaopu, Potter, James J
• Format: Article
• Language: English
• Subjects: Apoptosis; Biochemistry; Biomedical and Life Sciences; Biotechnology; Cells, Cultured; Cellular biology; Collagen Type I - antagonists & inhibitors; Collagen Type I - biosynthesis; Hepatic Stellate Cells - cytology; Hepatic Stellate Cells - drug effects; Hepatic Stellate Cells - metabolism; Humans; Life Sciences; Liver; Nutrition; Oncology; Peroxidation; Procollagen - antagonists & inhibitors; Procollagen - biosynthesis; Selenium; Sodium Selenite - pharmacology; Structure-Activity Relationship; Vitamin E; Vitamin E - pharmacology
• ISSN: 0163-4984; 1559-0720
• DOI: 10.1007/s12011-010-8672-7

This study investigated the effects of sodium selenite (Se) and of vitamin E (d-α-tochopherol) on the deposition of type I collagen by human LX-2 stellate cells. The cultured cells were treated with or without Se or vitamin E and with or without transforming growth factor β1 (TGFβ1). The combination of Se and vitamin E, but not either alone, protected against hepatic fibrosis by decreasing TGFβ1-mediated collagen secretion and accumulation by the stellate cells. This protective effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen. Effects of Se and vitamin E in decreasing α₁(I) collagen mRNA and increasing apoptosis of stellate cells indicate decreased formation of collagen, while decreases in transglutaminase 2, which catalyze cross-linking of collagen, lead to decreased stability of the secreted collagen. Effects of Se and vitamin E on reducing tissue inhibitor metalloproteinase 1 (TIMP-1) are associated with increased degradation. The combination of Se and vitamin E decreased lipid peroxidation, while Se alone increased the activity of the antioxidant enzyme thioredoxin reductase. In conclusion, the combination of Se and vitamin E protected against TGFβ1-mediated hepatic fibrosis by decreasing TGFβ1-mediated type I collagen accumulation by stellate cells. This effect is due to a combination of decreased formation, decreased stability and increased degradation of the collagen.