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Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway
- Source :
-
Toxicology & Applied Pharmacology . Feb2009, Vol. 235 Issue 1, p57-67. 11p. - Publication Year :
- 2009
-
Abstract
- Abstract: Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H2O2 production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice. [Copyright &y& Elsevier]
Details
- Language :
- English
- ISSN :
- 0041008X
- Volume :
- 235
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Toxicology & Applied Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 36433844
- Full Text :
- https://doi.org/10.1016/j.taap.2008.11.007