Kosenko E, Kaminsky Y, Lopata O, Muravyov N, Kaminsky A, Hermenegildo C, Felipo V
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Russia.
Metab Brain Dis. 1998 Mar;13(1):29-41. doi: 10.1023/a:1020626928259.
Injection of large doses of ammonium salts leads to the rapid death of animals. However, the molecular mechanisms involved in ammonia toxicity remain to be clarified. We reported that injecting ammonium acetate (7 mmol/kg) to rats increases the production of superoxide and reduces the activities of some antioxidant enzymes in rat liver and brain. We proposed that these effects induced by ammonia intoxication would be mediated by formation of nitric oxide. To test this possibility we tested whether injection of nitroarginine, an inhibitor of nitric oxide synthase, prevents the effects of ammonia intoxication on antioxidant enzymes and superoxide formation. Following injection of ammonia, glutathione peroxidase, superoxide dismutase and catalase activities were decreased in liver by 42%, 54% and 44%, respectively. In brain these activities were reduced by 35%, 46% and 65%, respectively. Glutathione reductase remained unchanged. Superoxide production in submitochondrial particles from liver and brain was increased by more than 100% in both tissues. Both reduction of activity of antioxidant enzymes and increased superoxide radical production were prevented by previous injection of 45 mg/kg of nitroarginine, indicating that ammonia induces increased formation of nitric oxide, which in turn reduces the activity of antioxidant enzymes, leading to increased formation of superoxide.
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。我们报道，给大鼠注射醋酸铵（7 mmol/kg）会增加超氧化物的产生，并降低大鼠肝脏和大脑中一些抗氧化酶的活性。我们提出，氨中毒所诱导的这些效应将由一氧化氮的形成介导。为了验证这种可能性，我们测试了一氧化氮合酶抑制剂硝基精氨酸的注射是否能预防氨中毒对抗氧化酶和超氧化物形成的影响。注射氨后，肝脏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分别降低了42%、54%和44%。在大脑中，这些活性分别降低了35%、46%和65%。谷胱甘肽还原酶保持不变。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。预先注射45 mg/kg的硝基精氨酸可防止抗氧化酶活性的降低和超氧化物自由基产生的增加，这表明氨诱导一氧化氮形成增加，进而降低抗氧化酶的活性，导致超氧化物形成增加。
