Sources of oxygen radicals in brain in acute ammonia intoxication in vivo.
The effects of acute ammonia intoxication on reactive oxygen species production by different sources in rat brain were studied. Ammonia intoxication in vivo leads to reduced activity of superoxide dismutase (SOD), catalase and glutathione peroxidase in brain nonsynaptic mitochondria and increased formation of O(2)(-) by submitochondrial particles. It also results in increased xanthine oxidase (XO) activity and decreased xanthine dehydrogenase (XDH)/XO activity ratio indicating conversion of XDH to XO and also increases monoamine oxidase A (MAO-A) activity but not of MAO-B. Blocking NMDA receptors with MK-801 prevents ammonia-induced oxidative stress, XDH to XO conversion and MAO-A activation. Ammonia intoxication did not lead to H(2)O(2) formation by mitochondria, in spite of increased O(2)(-) generation. The main source of H(2)O(2) in the mitochondrial matrix was Mn-SOD. Ammonia intoxication in vivo leads to increased superoxide and decreased hydrogen peroxide in nonsynaptic brain mitochondria. Increased superoxide is due to increased formation by the respiratory chain and by xanthine and aldehyde oxidases and decreased elimination by antioxidant enzymes. The reduced formation of hydrogen peroxide is due to the reduced activity of Mn-SOD. Prevention of ammonia-induced production of reactive oxygen species by MK-801 supports the idea that it is mediated by activation of NMDA receptors.
Kosenko
Elena
E
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, 142290 Russia.
Venediktova
Natalia
N
Kaminsky
Yury
Y
Montoliu
Carmina
C
Felipo
Vicente
V
D042931:Aldehyde Oxidase; D000445:Aldehyde Oxidoreductases; D000641:Ammonia / Q000506:poisoning*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D001923:Brain Chemistry; D002374:Catalase / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D017382:Reactive Oxygen Species; D013481:Superoxides; D016291:Dizocilpine Maleate; D000641:Ammonia; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D000445:Aldehyde Oxidoreductases; D042931:Aldehyde Oxidase; D008995:Monoamine Oxidase; D005980:Glutathione Reductase