Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway

Toxicol Appl Pharmacol. 2009 Feb 15;235(1):57-67. doi: 10.1016/j.taap.2008.11.007. Epub 2008 Nov 21.

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 beta-cell damage. Treatment of RIN cells with IL-1beta and IFN-gamma induced beta-cell damage through a NF-kappaB-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-kappaB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H(2)O(2) 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Line
  • Cytokines / toxicity*
  • Diabetes Mellitus, Experimental / chemically induced
  • Diabetes Mellitus, Experimental / prevention & control
  • Diabetes Mellitus, Type 1 / chemically induced
  • Diabetes Mellitus, Type 1 / prevention & control
  • Glucose / pharmacology
  • Insulin / metabolism
  • Insulin Secretion
  • Islets of Langerhans / drug effects*
  • Isothiocyanates
  • Male
  • Mice
  • Mice, Inbred ICR
  • NF-kappa B / metabolism*
  • Nitric Oxide
  • Rats
  • Rats, Sprague-Dawley
  • Specific Pathogen-Free Organisms
  • Streptozocin / toxicity*
  • Thiocyanates / pharmacology*

Substances

  • Cytokines
  • Insulin
  • Isothiocyanates
  • NF-kappa B
  • Thiocyanates
  • Nitric Oxide
  • Streptozocin
  • sulforafan
  • Glucose