Some biochemical and pathophysiological aspects of long-term elevation of brain ornithine concentrations.
Mice and chicken were given 5-fluoromethylornithine (5FMOrn), a selective inactivator of ornithine aminotransferase (OAT) over extended periods of time. This treatment allowed us to maintain elevated concentrations of ornithine in all tissues. Since gyrate atrophy, an autosomal recessive human disease, is characterized by the absence of OAT, special emphasis was put on the study of the visual system. Ophthalmoscopic and histologic examinations of the eye as well as electroretinograms and locomotor behaviour demonstrated an unimpaired visual system and brain. No toxic effects were observable in the treated mice. Likewise, chick embryo development was normal in spite of highly elevated brain and tissue ornithine concentrations. A likely explanation for the absence of toxic effects of 5FMOrn treatment, disregarding the non-toxicity of ornithine, is the fact that 10-20% of tissue OAT is refractory to inactivation by 5FMOrn. This residual activity may be sufficient to maintain vital functions.
Daune-Anglard
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G
Marion Merrell Dow Research Institute, Strasbourg, France.
Bonaventure
N
N
Seiler
N
N
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002336:Carnosine / Q000031:analogs & derivatives / Q000378:metabolism; D002645:Chickens; D004195:Disease Models, Animal; D004596:Electroretinography / Q000187:drug effects; D005123:Eye / Q000187:drug effects / Q000378:metabolism; D005260:Female; D015799:Gyrate Atrophy / Q000378:metabolism* / Q000503:physiopathology; D008137:Longitudinal Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D009952:Ornithine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000633:toxicity; D009953:Ornithine-Oxo-Acid Transaminase / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
C057405:5-fluoromethylornithine; D005680:gamma-Aminobutyric Acid; D002336:Carnosine; D009952:Ornithine; D009953:Ornithine-Oxo-Acid Transaminase