Indole-3-carbinol alleviates carbon tetrachloride-induced liver injury by inhibiting inflammatory response and regulating lipid metabolism

Abstract

The hepatoprotective effects of indole-3-carbinol (I3C), one of the byproducts of the breakdown of glucosinolate glucobrassicin, were examined in mice with carbon tetrachloride (CCl4)-induced hepatotoxicity. I3C was administered orally at a dose of 50 or 100 mg/kg to C57BL/6 mice for 3 consecutive days with or without a subsequent single oral administration of CCl4 (1.5 mL/kg). I3C treatment significantly suppressed the increases in alanine aminotransferase and aspartate aminotransferase levels in the sera of CCl4-injured mice. In addition, I3C treatment markedly suppressed CCl4-induced hepatic inflammation, by suppressing the activation of macrophages and Kupffer cells in the liver. To examine the effects of I3C on lipid accumulation, 3T3-L1 pre-adipocytes were differentiated with I3C or vehicle control. I3C treatment reduced lipid accumulation, which appeared to be associated with the downregulation of adipogenic transcription factors, such as CCAAT/enhancer-binding protein α, peroxisome proliferator-activated receptor γ, and lipid accumulation-related genes, including adipocyte protein-2. Taken together, the present study suggest that I3C treatment reduces hepatocyte death and lipid accumulation in hepatocytes in CCl4-induced hepatic injury with concurrent suppression of macrophages/Kupffer cells, which was further evidenced by I3C-treated pre-adipocytes in vitro, through downregulation of lipid metabolism.