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

Changming Yang; Xianqiong Gong; Qing Ai; Pu Ge; Ling Lin; Li Zhang

doi:10.1016/j.intimp.2015.02.018

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

Int Immunopharmacol. 2015 Apr;25(2):393-9. doi: 10.1016/j.intimp.2015.02.018. Epub 2015 Feb 21.

Authors

Changming Yang¹, Xianqiong Gong², Qing Ai³, Pu Ge⁴, Ling Lin⁴, Li Zhang⁵

Affiliations

¹ Department of Anesthesiology, The First People's Hospital of Jingmen, Jingmen, Hubei Province, China.
² Hepatology Center, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, China.
³ Department of Physiology, Chongqing Medical University, Chongqing, China.
⁴ Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
⁵ Department of Pathophysiology, Chongqing Medical University, Chongqing, China. Electronic address: zhangli@cqmu.edu.cn.

PMID: 25711693
DOI: 10.1016/j.intimp.2015.02.018

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.

Keywords: AICAR; AMP-activated protein kinase; Carbon tetrachloride; Hepatitis; Inflammation.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Alanine Transaminase / blood
Aminoimidazole Carboxamide / analogs & derivatives*
Aminoimidazole Carboxamide / pharmacology
Aminoimidazole Carboxamide / therapeutic use
Animals
Anti-Inflammatory Agents / pharmacology
Anti-Inflammatory Agents / therapeutic use*
Aspartate Aminotransferases / blood
Carbon Tetrachloride Poisoning / blood
Carbon Tetrachloride Poisoning / drug therapy*
Carbon Tetrachloride Poisoning / metabolism
Chemical and Drug Induced Liver Injury / blood
Chemical and Drug Induced Liver Injury / drug therapy*
Chemical and Drug Induced Liver Injury / metabolism
Hepatitis / blood
Hepatitis / drug therapy*
Hepatitis / metabolism
Interleukin-6 / blood
Interleukin-6 / 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
Ribonucleosides / therapeutic use*
Tumor Necrosis Factor-alpha / blood
Tumor Necrosis Factor-alpha / genetics

Substances

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