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The present work investigated the <jats:italic>in vitro<\/jats:italic> effects of ornithine and homocitrulline on important parameters of oxidative stress in cerebral cortex from young rats. Ornithine significantly increased chemiluminescence and thiobarbituric acid\u2010reactive substances levels, indicators of lipid peroxidation, while homocitrulline only augmented chemiluminescence values. Furthermore, ornithine\u2010induced increase of thiobarbituric acid\u2010reactive substances levels was attenuated (melatonin and reduced glutathione) or totally prevented (\u03b1\u2010tocopherol) by free radical scavengers, suggesting that reactive species were involved in the lipid oxidative damage. We also observed that ornithine and homocitrulline significantly decreased the tissue antioxidant defenses, determined by reduced glutathione concentrations, the major non\u2010enzymatic antioxidant defense found in the brain. Homocitrulline reduction of glutathione levels was completely prevented by melatonin and \u03b1\u2010tocopherol, whereas ornithine\u2010induced decrease of glutathione levels was only attenuated by these free radical scavengers. Ornithine and homocitrulline also induced protein oxidative damage, increasing carbonyl formation and sulfhydryl oxidation. In contrast, these amino acids did not affect nitric oxide production, indicating that nitrogen reactive species were not implicated in the lipid and oxidative damage provoked by ornithine and homocitrulline. Therefore, it is presumed that the major metabolites accumulating in hyperornithinemia\u2013hyperammonemia\u2013homocitrullinuria syndrome elicit oxidative stress and that this pathomechanism may possibly be involved in the brain damage found in patients affected by this disorder.<\/jats:p>","DOI":"10.1016\/j.ijdevneu.2009.08.004","type":"journal-article","created":{"date-parts":[[2009,8,14]],"date-time":"2009-08-14T09:45:00Z","timestamp":1250243100000},"page":"635-641","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Evidence that the major metabolites accumulating in hyperornithinemia\u2013hyperammonemia\u2013homocitrullinuria syndrome induce oxidative stress in brain of young rats"],"prefix":"10.1002","volume":"27","author":[{"given":"Alexandre Umpierrez","family":"Amaral","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica Instituto de Ci\u00eancias B\u00e1sicas da Sa\u00fade 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