2-Methoxyestradiol attenuates liver fibrosis in mice: implications for M2 macrophages.

Abstract

Liver fibrosis is a major health problem worldwide due to its serious complications including cirrhosis and liver cancer. 2-Methoxyestradiol (2-ME) is an end metabolite of estradiol with anti-proliferative, antioxidant, and anti-inflammatory activities. However, the protective role of 2-ME in liver fibrosis has not been fully investigated. The aim of this study was to determine the protective effect of 2-ME in carbon tetrachloride (CCl4)-induced liver fibrosis in mice. Animals were injected intraperitoneally with CCl4 twice weekly for 6weeks. 2-ME 50mg/kg or 100mg/kg was administrated intraperitoneally every day over the same period. Our data showed that 2-ME reduced the extent of liver toxicity and fibrosis due to CCl4 exposure. It restored the elevated serum liver enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) levels and ameliorated oxidative status. In addition, 2-ME significantly reduced collagen deposition and alpha-smooth muscle actin (α-SMA) protein expressions. Furthermore, 2-ME markedly lowered macrophage infiltration and macrophage alternative activation marker chitinase-like molecules (CHI3L3/YM1). The results of this study indicate an important protective activity of 2-ME in liver fibrosis and highlight the role of macrophage recruitment and alternative activation as a possible target.