Caloric restriction mimetic 2-deoxyglucose alleviated lethal liver injury induced by lipopolysaccharide/D-galactosamine in mice.
The glycolytic inhibitor 2-deoxyglucose (2-DG) is a calorie restriction (CR) mimetic produces CR-like beneficial effects in both acute and chronic pathological processes, but whether 2-DG is also helpful in critical and life-threatening situation is not known. In the present study, the potential benefits of 2-DG in lipopolysaccharide/D-galactosamine (LPS/D-Gal)-induced lethal liver injury were investigated. The results indicated that treatment with 2-DG suppressed the elevation of plasma aminotransferases, alleviated the histopathological abnormalities and improved the survival rate of LPS/D-Gal-exposed mice. Treatment with 2-DG also suppressed the production of pro-apoptotic cytokine TNF-α, the phosphorylation of JNK, the activation of caspase cascade and the count of TUNEL-positive apoptotic hepatocytes. These data suggested that the CR mimetic 2-DG could also provide beneficial effects in lethal pathological process such as LPS/D-Gal-induced fulminant liver injury.
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Qian
Q
Che
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Ling
L
Lin
Department of Physiology, Chongqing Medical University, Chongqing, China.
Qing
Q
Ai
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Pu
P
Ge
Hospital of Chongqing University of Arts and Sciences, Chongqing, China.
Jie
J
Dai
Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China.
Rong
R
Jiang
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Dan
D
Zhou
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Jingyuan
J
Wan
Department of Pathophysiology, Chongqing Medical University, Chongqing, China; Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University, Chongqing, China. Electronic address: zhangli@cqmu.edu.cn.
Li
L
Zhang
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D032701:Biomimetics; D031204:Caloric Restriction; D020169:Caspases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D003847:Deoxyglucose / Q000008:administration & dosage / Q000494:pharmacology*; D005688:Galactosamine / Q000633:toxicity; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000633:toxicity; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D005688:Galactosamine; D003847:Deoxyglucose; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020169:Caspases
2-Deoxyglucose; Calorie restriction mimetic; Lipopolysaccharide; Liver injury