Vitamin D inhibits development of liver fibrosis in an animal model but cannot ameliorate established cirrhosis.

Abstract

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.

• Authors: Shirley Abramovitch, Efrat Sharvit, Yosef Weisman, Amir Bentov, Eli Brazowski, Gili Cohen, Oded Volovelsky, Shimon Reif
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 308 Issue 2 Pg. G112-20 (Jan 15 2015) ISSN: 1522-1547 [Electronic] United States
• PMID: 25214398 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 the American Physiological Society.

Chemical References

• Thioacetamide
• Vitamin D

Topics

• Animals
• Cell Proliferation (drug effects)
• Disease Models, Animal
• Fibrosis (chemically induced, metabolism, pathology)
• Hepatic Stellate Cells (drug effects, metabolism)
• Liver Cirrhosis (metabolism, pathology)
• Liver Cirrhosis, Experimental (chemically induced, metabolism)
• Male
• Rats, Wistar
• Thioacetamide (pharmacology)
• Vitamin D (metabolism)