Involvement of catalase in the protective benefits of metformin in mice with oxidative liver injury.
Metformin is a commonly used anti-diabetic drug with AMP-activated protein kinase (AMPK)-dependent hypoglycemic activities. Recent studies have revealed its anti-inflammatory and anti-oxidative properties. In the present study, the anti-oxidative potential of metformin and its potential mechanisms were investigated in a mouse model with carbon tetrachloride (CCl₂)-induced severe oxidative liver injury. Our results showed that treatment with metformin significantly attenuated CCl₂-induced elevation of serum aminotransferases and hepatic histological abnormalities. The alleviated liver injury was associated with decreased hepatic contents of oxidized glutathione (GSSG) and malondialdehyde (MDA). In addition, metformin treatment dose-dependently enhanced the activities of catalase (CAT) and decreased CCl₄-induced elevation of hepatic H₂O₂ levels, but it had no obvious effects on the protein level of CAT. We also found that metformin increased the level of phosphorylated AMP-activated protein kinase (AMPK), but treatment with AMPK activator AICAR had no obvious effects on CAT activity. A molecular docking analysis indicated that metformin might interact with CAT via hydrogen bonds. These data suggested that metformin effectively alleviated CCl₄-induced oxidative liver injury in mice and these hepatoprotective effects might be associated with CAT.
Hospital of Chongqing University of Arts and Sciences, Chongqing, China.
Jie
J
Dai
Laboratory of Clinical Diagnosis, Chongqing Medical University, Chongqing, China.
Mingwei
M
Liu
Department of Physiology, Chongqing Medical University, Chongqing, China.
Qing
Q
Ai
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Ling
L
Lin
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Kunwei
K
Wu
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Xinyu
X
Deng
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Yuping
Y
Jing
Department of Pathophysiology, Chongqing Medical University, Chongqing, China.
Mengying
M
Jia
Department of Pharmacology, Chongqing Medical University, Chongqing, China.
Jingyuan
J
Wan
Department of Pathophysiology, Chongqing Medical University, Chongqing, China. Electronic address: zhangli@cqmu.edu.cn.
Li
L
Zhang
D000818:Animals; D002252:Carbon Tetrachloride Poisoning; D002374:Catalase / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000201:enzymology*; D004797:Enzyme-Linked Immunosorbent Assay; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D015151:Immunoblotting; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008687:Metformin / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D018384:Oxidative Stress; D011485:Protein Binding; D011487:Protein Conformation; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D007004:Hypoglycemic Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D008687:Metformin; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase
AMPK; Carbon tetrachloride; Catalase; Metformin; Oxidative stress