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

Abstract

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.

• Authors: Changming Yang, Xianqiong Gong, Qing Ai, Pu Ge, Ling Lin, Li Zhang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 25 Issue 2 Pg. 393-9 (Apr 2015) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 25711693 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin-6
• RNA, Messenger
• Ribonucleosides
• Tumor Necrosis Factor-alpha
• Nitric Oxide
• Aminoimidazole Carboxamide
• acadesine
• Peroxidase
• Nitric Oxide Synthase Type II
• Nos2 protein, mouse
• Aspartate Aminotransferases
• Alanine Transaminase
• Matrix Metalloproteinase 3
• Mmp3 protein, mouse
• Matrix Metalloproteinase 2
• Mmp2 protein, mouse
• Matrix Metalloproteinase 9
• Mmp9 protein, mouse

Topics

• Alanine Transaminase (blood)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology, therapeutic use)
• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Aspartate Aminotransferases (blood)
• Carbon Tetrachloride Poisoning (blood, drug therapy, metabolism)
• Chemical and Drug Induced Liver Injury (blood, drug therapy, metabolism)
• Hepatitis (blood, drug therapy, metabolism)
• Interleukin-6 (blood, genetics)
• Liver (metabolism)
• Male
• Matrix Metalloproteinase 2 (genetics)
• Matrix Metalloproteinase 3 (genetics)
• Matrix Metalloproteinase 9 (genetics)
• Mice, Inbred BALB C
• Nitric Oxide (blood)
• Nitric Oxide Synthase Type II (genetics)
• Peroxidase (metabolism)
• RNA, Messenger (metabolism)
• Ribonucleosides (pharmacology, therapeutic use)
• Tumor Necrosis Factor-alpha (blood, genetics)