锰福地吡预防对乙酰氨基酚诱导的小鼠肝损伤。
Mangafodipir prevents liver injury induced by acetaminophen in the mouse.
作者信息
Bedda Sassia, Laurent Alexis, Conti Filomena, Chéreau Chistiane, Tran Agnès, Tran-Van Nhieu Jeanne, Jaffray Patrick, Soubrane Olivier, Goulvestre Claire, Calmus Yvon, Weill Bernard, Batteux Frédéric
机构信息
Laboratoire d'Immunologie, UPRES 1833, Faculté Cochin, Pavillon Hardy, Université Paris V, AP-HP, 75679 Paris Cedex 14, France.
出版信息
J Hepatol. 2003 Nov;39(5):765-72. doi: 10.1016/s0168-8278(03)00325-8.
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.
背景/目的：急性肝衰竭（ALF）以大量肝细胞坏死为特征，常由药物中毒引起，尤其是对乙酰氨基酚（APAP）。肝细胞坏死是由于APAP的代谢产物NAPQI导致谷胱甘肽耗竭以及活性氧（ROS）过度产生引起的线粒体损伤所致。考虑到目前用于肝脏磁共振成像的造影剂锰福地匹尔的结构，我们推测该分子可能具有抗氧化活性，并有可能用于治疗APAP诱导的ALF。
方法/结果：锰福地匹尔具有超氧化物歧化酶、过氧化氢酶和谷胱甘肽还原酶活性。它可以抑制培养的肝细胞产生ROS，并保护这些细胞免受黄嘌呤氧化酶、H₂O₂或紫外线诱导的氧化应激。此外，对APAP诱导的ALF小鼠进行预防性或治疗性给予锰福地匹尔可显著提高存活率，并消除天冬氨酸转氨酶升高和组织学损伤。
结论
这些数据表明锰福地匹尔在治疗人类中毒性ALF方面具有潜在的应用价值。
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