Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.
1,25(OH)2D3, the active form of vitamin D, has an antiproliferative and antifibrotic effect on hepatic stellate cells. Our aim was to investigate the potential of 1,25(OH)2D3 to inhibit the development of liver fibrosis and to ameliorate established fibrosis in vivo. The antifibrotic effect of 1,25(OH)2D3 was investigated in a thioacetamide (TAA) model (as a preventive treatment and as a remedial treatment) and in a bile duct ligation model. In the preventive model, rats received simultaneously intraperitoneum injection of TAA and/or 1,25(OH)2D3 for 10 wk. In the remedial model, rats were treated with TAA for 10 wk and then received 1,25(OH)2D3 or saline for 8 wk. Fibrotic score was determined by Masson staining. Collagen I, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP1), platelet-derived growth factor (PDGF), and transforming growth factor-β (TGF-β) expression were measured by Western blot analysis and real-time PCR. Hypercalemia was detected by chemistry measurements. Preventive treatment of 1,25(OH)2D3 significantly suppressed liver fibrosis both macroscopically and microscopically and significantly lowered the fibrotic score of the TAA + 1,25(OH)2D3 group compared with the TAA group. 1,25(OH)2D3 significantly inhibited expression of PDGF and TGF-β by ∼50% and suppressed the expression of collagen Iα1, TIMP1, and α-SMA by approximately three-, two-, and threefold, respectively. In contrast, 1,25(OH)2D3 was inefficient in amelioration of established liver fibrosis. Administration of 1,25(OH)2D3 to bile duct ligation rats led to a high mortality rate probably caused by hypercalcemia. We conclude that 1,25(OH)2D3 may be considered as a potential preventive treatment in an in vivo model but failed to ameliorate established cirrhosis.
['Abramovitch|Shirley|S|', 'Sharvit|Efrat|E|', 'Weisman|Yosef|Y|', 'Bentov|Amir|A|', 'Brazowski|Eli|E|', 'Cohen|Gili|G|', 'Volovelsky|Oded|O|', 'Reif|Shimon|S|']
D000818:Animals D049109:Cell Proliferation D004195:Disease Models, Animal D005355:Fibrosis D055166:Hepatic Stellate Cells D008103:Liver Cirrhosis D008106:Liver Cirrhosis, Experimental D008297:Male D017208:Rats, Wistar D013853:Thioacetamide D014807:Vitamin D
vitamin D liver fibrosis thioacetamide collagen