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Dehydroepiandrosterone modulates nuclear factor-kappaB activation in hippocampus of diabetic rats.

Authors: Aragno, M  Mastrocola, R  Brignardello, E  Catalano, M  Robino, G  Manti, R  Parola, M  Danni, O  Boccuzzi, G 
Citation: Aragno M, etal., Endocrinology 2002 Sep;143(9):3250-8.
Pubmed: (View Article at PubMed) PMID:12193536
DOI: Full-text: DOI:10.1210/en.2002-220182

Oxidative stress induced by chronic hyperglycemia contributes to cerebrovascular complications in diabetes. Reactive oxygen species activate the transcription factor nuclear factor-kappaB (NF-kappaB), which in turn activates a variety of target genes linked to the development of diabetic complications. Dehydroepiandrosterone, an adrenal steroid, which possesses a multitargeted antioxidant effects, is also synthesized de novo by the brain. Normoglycemic and streptozotocin-diabetic rats were either treated with dehydroepiandrosterone (DHEA) for 7, 14, or 21 d (4 mg/d per rat) or left untreated. Oxidative state, antioxidant balance and activation of nuclear transcriptional redox-sensitive factor NF-kappaB were evaluated in the hippocampus area. In streptozotocin-treated rats, besides the strong increase in oxygen reactive species, there is also a persistent activation of NF-kappaB. The derangement of the oxidative balance in the brain induced by diabetes improves with DHEA. Moreover, DHEA completely counteracts NF-kappaB activation, measured as DNA binding activity, and hinders the increase of IkappaB-alpha inhibitory subunit induced by oxidative stress. The time-lag of DHEA's effects on NF-kappaB activation parallels its effects on oxidative balance. Results indicate that DHEA might protect hippocampus from chronic activation of NF-kappaB-dependent genes by reducing NF-kappaB nuclear translocation. This could result in protection from diabetes-dependent brain damage.

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RGD Object Information
RGD ID: 625669
Created: 2002-10-28
Species: All species
Last Modified: 2002-10-28
Status: ACTIVE



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