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.
journal_name
J Inherit Metab Disjournal_title
Journal of inherited metabolic diseaseauthors
Latini A,Scussiato K,Leipnitz G,Gibson KM,Wajner Mdoi
10.1007/s10545-007-0599-6subject
Has Abstractpub_date
2007-10-01 00:00:00pages
800-10issue
5eissn
0141-8955issn
1573-2665journal_volume
30pub_type
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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abstract::Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid beta-glucosidase. The most prevalent mutant genotype in type I Gaucher disease, N370S/N370S, is commonly thought to confer a mild phenotype presenting in adulthood. To characterize a subset of more severely affected N370S homozyg...
journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1023/a:1005372730310
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
doi:10.1007/BF01800711
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:1990-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1023/a:1010319001722
更新日期:2001-04-01 00:00:00
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章,评审
doi:10.1007/s10545-006-0251-x
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
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abstract:: ...
journal_title:Journal of inherited metabolic disease
pub_type: 社论
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
pub_type: 杂志文章
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更新日期:2003-01-01 00:00:00
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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journal_title:Journal of inherited metabolic disease
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