S-allylmercapto-N-acetylcysteine up-regulates cellular glutathione and protects vascular endothelial cells from oxidative stress

Nira Izigov, Nahid Farzam, Naphtali Savion

Research output: Contribution to journalArticlepeer-review

Abstract

Oxidative stress and/or low cellular glutathione (GSH) levels are associated with the development and progression of numerous pathological conditions. Cells possess various antioxidant protection mechanisms, including GSH and phase II detoxifying enzymes. N-acetylcysteine (NAC) supplies cells with cysteine to increase GSH level but its efficacy is relatively low because of its limited tissue penetration. Allicin (diallyl thiosulfinate), a reactive sulfaorganic compound, increases cellular GSH and phase II detoxifying enzymes in vascular endothelial cells (EC). A novel compound was designed: S-allylmercapto-N-acetylcysteine (ASSNAC), a conjugate of S-allyl mercaptan (a component of allicin) and NAC. Both ASSNAC and NAC increased cellular GSH of ECs, reaching a maximum of up to four- and threefold increase after exposure for 24 or 6 h at a concentration of 0.2 or 1 mM, respectively. ASSNAC induced nuclear translocation of the activated transcription factor Nrf2 and expression of phase II detoxifying enzymes. EC exposure to tBuOOH resulted in 75% cytotoxicity, and pretreatment of cultures with 0.2 mM ASSNAC or 2 mM NAC reduced cytotoxicity to 20 and 42%, respectively. In conclusion, ASSNAC is superior to NAC in protecting cells from oxidative stress because of its ability to up-regulate both GSH and the expression of phase II detoxifying enzymes.

Original languageEnglish
Pages (from-to)1131-1139
Number of pages9
JournalFree Radical Biology and Medicine
Volume50
Issue number9
DOIs
StatePublished - 1 May 2011

Keywords

  • Cytotoxicity
  • Endothelial cells
  • Free radicals
  • Gene expression
  • Glutamate-cysteine- ligase modifier subunit
  • Glutathione
  • N-acetylcysteine
  • Nuclear factor erythroid 2-related factor-2
  • Reactive oxygen species
  • S-allylmercapto-N-acetylcysteine

Fingerprint

Dive into the research topics of 'S-allylmercapto-N-acetylcysteine up-regulates cellular glutathione and protects vascular endothelial cells from oxidative stress'. Together they form a unique fingerprint.

Cite this