Kosenko E, Kaminsky Y, Kaminsky A, Valencia M, Lee L, Hermenegildo C, Felipo V
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Russia.
Free Radic Res. 1997 Dec;27(6):637-44. doi: 10.3109/10715769709097867.
Injection of large doses of ammonium salts lead to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We have tested the effect of injecting 7 mmol/kg of ammonium acetate on the production of superoxide and on the activities of some antioxidant enzymes in rat liver, brain, erythrocytes and plasma. Glutathione peroxidase, superoxide dismutase and catalase activities were decreased in liver and brain (both in cytosolic and mitochondrial fractions) and also in blood red cells, while glutathione reductase activity remained unchanged. Superoxide production in submitochondrial particles from liver and brain was increased by more than 100% in both tissues. Both diminished activity of antioxidant enzymes and increased superoxide radical production could lead to oxidative stress and cell damage, which could be involved in the mechanism of acute ammonia toxicity.
注射大剂量铵盐会导致动物迅速死亡。然而,氨毒性所涉及的分子机制仍有待阐明。我们测试了注射7 mmol/kg醋酸铵对大鼠肝脏、大脑、红细胞和血浆中超氧化物产生以及一些抗氧化酶活性的影响。肝脏和大脑(细胞质和线粒体部分)以及红细胞中的谷胱甘肽过氧化物酶、超氧化物歧化酶和过氧化氢酶活性均降低,而谷胱甘肽还原酶活性保持不变。肝脏和大脑亚线粒体颗粒中的超氧化物产生在两个组织中均增加了100%以上。抗氧化酶活性的降低和超氧自由基产生的增加都可能导致氧化应激和细胞损伤,这可能参与急性氨毒性的机制。