1. Mangafodipir prevents liver injury induced by acetaminophen in the mouse
- Author
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Sassia Bedda, Patrick Jaffray, Alexis Laurent, Filomena Conti, Chistiane Chéreau, Frédéric Batteux, Jeanne Tran Van Nhieu, Claire Goulvestre, Yvon Calmus, Bernard Weill, Olivier Soubrane, and Agnès Tran
- Subjects
Carcinoma, Hepatocellular ,NAPQI ,Glutathione reductase ,Pharmacology ,Antioxidants ,Superoxide dismutase ,Mice ,chemistry.chemical_compound ,Superoxides ,Cell Line, Tumor ,medicine ,Mangafodipir ,Animals ,Humans ,fas Receptor ,Xanthine oxidase ,Edetic Acid ,Acetaminophen ,chemistry.chemical_classification ,Liver injury ,Mice, Inbred BALB C ,Reactive oxygen species ,Hepatology ,biology ,Caspase 3 ,Liver Neoplasms ,digestive, oral, and skin physiology ,Antibodies, Monoclonal ,Cytochromes c ,Liver Failure, Acute ,medicine.disease ,Caspase Inhibitors ,Glutathione ,Survival Analysis ,Enzymes ,Liver ,Biochemistry ,chemistry ,Pyridoxal Phosphate ,biology.protein ,Female ,Oxidoreductases ,Reactive Oxygen Species ,medicine.drug - Abstract
Background/Aims : Acute liver failure (ALF), characterized by massive hepatocyte necrosis, is often caused by drug poisoning, particularly with acetaminophen (APAP). Hepatocyte necrosis is consecutive to glutathione depletion by NAPQI, a metabolite of APAP, and to mitochondrial damages caused by reactive oxygen species (ROS) overproduction. Considering the structure of Mangafodipir, a contrast agent currently used in magnetic resonance imaging of the liver, we hypothesized that this molecule could exert an antioxidant activity and be possibly used as a treatment of APAP-induced ALF. Methods/Results : Mangafodipir is endowed with superoxide dismutase, catalase, and glutathione reductase activities. It can inhibit ROS production by hepatocytes in culture, and protect those cells from oxidative stresses induced by exposure to xanthine oxidase, H 2 O 2 , or UV light. Moreover, preventive or curative administration of Mangafodipir to mice with APAP-induced ALF significantly increases survival rates, and abrogates aspartate aminotransferase elevation and histological damage. Conclusions : Those data point out the potential interest of Mangafodipir in the treatment of toxic ALF in humans.
- Published
- 2003