Kosenko E, Kaminski Y, Lopata O, Muravyov N, Felipo V
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Russia.
Free Radic Biol Med. 1999 Jun;26(11-12):1369-74. doi: 10.1016/s0891-5849(98)00339-6.
Acute ammonia intoxication diminishes the activities of antioxidant enzymes and increases superoxide formation in brain. These effects could play a role in the mechanism of ammonia toxicity. It has been shown that ammonia toxicity is mediated by activation of NMDA receptors. The aim of this work was to assess whether ammonia-induced changes in antioxidant enzymes and in superoxide formation are mediated by activation of NMDA receptors. It is shown that MK-801, an antagonist of NMDA receptors prevents ammonia-induced changes in superoxide dismutase, glutathione peroxidase and catalase. Ammonia intoxication also induces a depletion of glutathione and an increase in lipid peroxidation. Both effects, as well as ammonia-induced increase in superoxide formation are prevented by MK-801. These results indicate that ammonia-induced oxidative stress in brain is mediated by excessive activation of NMDA receptors and support the idea that oxidative stress can play a role in the mechanism of ammonia toxicity.
急性氨中毒会降低大脑中抗氧化酶的活性并增加超氧化物的形成。这些效应可能在氨毒性机制中发挥作用。已有研究表明，氨毒性是由NMDA受体的激活介导的。本研究的目的是评估氨诱导的抗氧化酶和超氧化物形成的变化是否由NMDA受体的激活介导。结果表明，NMDA受体拮抗剂MK-801可防止氨诱导的超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶的变化。氨中毒还会导致谷胱甘肽耗竭和脂质过氧化增加。MK-801可预防这两种效应以及氨诱导的超氧化物形成增加。这些结果表明，大脑中氨诱导的氧化应激是由NMDA受体的过度激活介导的，并支持氧化应激可能在氨毒性机制中起作用的观点。
