title: 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside-attenuates LPS/D-Gal-induced acute hepatitis in mice.
abstract: The AMP-activated protein kinase (AMPK)-mediated energy-sensing signals play important roles in reprogramming the expression of inflammatory genes. In the present study, the potential effects of the AMPK activator 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR) were investigated in a mouse model with LPS/D-Gal-induced acute hepatitis. Our experimental data indicated that treatment with AICAR suppressed the elevation of plasma aminotransferases and alleviated the histopathological abnormalities in mice exposed to LPS/D-Gal. Treatment with AICAR also inhibited the LPS/D-Gal-induced up-regulation of TNF-α, NO and myeloperoxidase. In addition, the LPS/D-Gal-induced expression of pro-apoptotic factor Bax, cleavage of caspase-3, elevation of hepatic caspase-3, caspase-8, caspase-9 activities and induction of terminal deoxynucleotidyl transferase-mediated nucleotide nick-end labeling-positive cells were all suppressed by AICAR. These results suggested that the AMPK activator AICAR could attenuate LPS/D-Gal-induced acute hepatitis, which implies that AMPK might become a novel target for the treatment of inflammation-based liver disorders.
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Physiology, Chongqing Medical University, Chongqing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Ai
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Lin
authors.affiliation: Hepatology Center, Xiamen Hospital of Traditional Chinese Medicine, Xiamen, Fujian Province, China.
authors.forename: Xianqiong
authors.initials: X
authors.lastname: Gong
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Pu
authors.initials: P
authors.lastname: Ge
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Che
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
authors.forename: Aiqing
authors.initials: A
authors.lastname: Wen
authors.affiliation: Department of Pathophysiology, Chongqing Medical University, Chongqing, China Laboratory of Stem cell and Tissue Engineering, Chongqing Medical University, Chongqing, China zhangli@cqmu.edu.cn.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors; D000620:Aminoimidazole Carboxamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D005690:Galactose / Q000276:immunology; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D058990:Molecular Targeted Therapy; D009569:Nitric Oxide / Q000378:metabolism; D012265:Ribonucleotides / Q000008:administration & dosage* / Q000494:pharmacology; D000637:Transaminases / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D007004:Hypoglycemic Agents; D008070:Lipopolysaccharides; D012265:Ribonucleotides; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D000620:Aminoimidazole Carboxamide; D000637:Transaminases; D055372:AMP-Activated Protein Kinases; D020169:Caspases; C031143:AICA ribonucleotide; D005690:Galactose
keywords: AICAR; AMPK; hepatitis; inflammation; lipopolysaccharide