5-Aminoimidazole-4-carboxamide-1-β-d-ribofuranoside alleviated carbon tetrachloride-induced acute hepatitis in mice

• AICAR significantly alleviated CCl4-induced liver damage.
• AICAR inhibited CCl4-induced upregulation of pro-inflammatory mediators.
• AICAR decreased CCl4-induced expression of matrix metalloproteinases.
• AICAR suppressed CCl4-induced nuclear accumulation of NF-κB.

AMP-activated protein kinase (AMPK) is one of the principal cellular energy sensors participating in maintenance of energy balance but recent evidences also suggested that AMPK might be involved in the regulation of inflammation. In the present study, the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) was used to investigate the potential roles of AMPK in carbon tetrachloride (CCl4)-induced acute hepatitis. The experimental data indicated that treatment with AICAR significantly decreased the elevation of plasma aminotransferases and alleviated hepatic histological abnormalities in CCl4-exposed mice. Treatment with AICAR also inhibited the increase of myeloperoxidase (MPO), the induction of TNF-α, IL-6, inducible nitric oxide synthase (iNOS), nitric oxide and the upregulation of matrix metalloproteinase 2 (MMP-2), MMP-3 and MMP-9 in mice exposed to CCl4. These effects were associated with suppressed nuclear accumulation of NF-κB p65. These results indicated that the AMPK activator AICAR effectively suppressed the inflammatory responses and alleviated liver damage induced by CCl4, implying that AMPK activation might be beneficial for ameliorating inflammation-based liver damage.