title: Evidence for oxidative stress in tissues derived from succinate semialdehyde dehydrogenase-deficient mice.
abstract: Animal models of inborn errors of metabolism are useful for investigating the pathogenesis associated with the corresponding human disease. Since the mechanisms involved in the pathophysiology of succinate semialdehyde dehydrogenase (SSADH) deficiency (Aldh5a1; OMIM 271980) are still not established, in the present study we evaluated the tissue antioxidant defences and lipid peroxidation in various cerebral structures (cortex, cerebellum, thalamus and hippocampus) and in the liver of SSADH-deficient mice. The parameters analysed were total radical-trapping antioxidant potential (TRAP) and glutathione (GSH) levels, the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), as well as thiobarbituric acid-reactive substances (TBARS). We first observed that the tissue nonenzymatic antioxidant defences were significantly reduced in the SSADH-deficient animals, particularly in the liver (decreased TRAP and GSH) and in the cerebral cortex (decreased GSH), as compared to the wild-type mice. Furthermore, SOD activity was significantly increased in the liver and cerebellum, whereas the activity of CAT was significantly higher in the thalamus. In contrast, GPx activity was significantly diminished in the hippocampus. Finally, we observed that lipid peroxidation (TBARS levels) was markedly increased in the liver and cerebral cortex, reflecting a high lipid oxidative damage in these tissues. Our data showing an imbalance between tissue antioxidant defences and oxidative attack strongly indicate that oxidative stress is involved in the pathophysiology of SSADH deficiency in mice, and likely the corresponding human disorder.
authors: Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Florianópolis, SC, Brazil.
authors: A
authors: A
authors: Latini
authors: K
authors: K
authors: Scussiato
authors: G
authors: G
authors: Leipnitz
authors: K M
authors: KM
authors: Gibson
authors: M
authors: M
authors: Wajner
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D020739:Brain Diseases, Metabolic, Inborn / Q000201:enzymology / Q000235:genetics / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002531:Cerebellum / Q000201:enzymology / Q000378:metabolism; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018384:Oxidative Stress; D050644:Succinate-Semialdehyde Dehydrogenase / Q000172:deficiency* / Q000235:genetics; D013482:Superoxide Dismutase / Q000378:metabolism; D013788:Thalamus / Q000201:enzymology / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000975:Antioxidants; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; C520316:Aldh5a1 protein, mouse; D050644:Succinate-Semialdehyde Dehydrogenase; D005978:Glutathione