Dehydroxymethylepoxyquinomicin (DHMEQ) can suppress tumour necrosis factor-α production in lipopolysaccharide-injected mice, resulting in rescuing mice from death in vivo

Clin Exp Immunol. 2011 Nov;166(2):299-306. doi: 10.1111/j.1365-2249.2011.04475.x.

Abstract

Dehydroxymethylepoxyquinomicin (DHMEQ), a new nuclear factor (NF)-κB inhibitor, has several beneficial effects, including the suppression of tumour growth and anti-inflammatory effects. DHMEQ can also suppress the production of tumour necrosis factor (TNF)-α induced by lipopolysaccharide (LPS) in vitro. In the present study, we examine the effects of DHMEQ on TNF-α production in vivo and on the survival of mice injected with LPS. When DHMEQ was injected into mice 2 h before LPS injection, the survival of the LPS-injected mice was prolonged. When DHMEQ was injected twice (2 h before LPS injection and the day after LPS injection), all the mice were rescued. The injection of DHMEQ 1 h after LPS injection and the day after LPS injection also resulted in the rescue of all mice. The serum levels of TNF-α in the mice that received both LPS and DHMEQ were suppressed compared to the mice that received only LPS. These results suggest that DHMEQ can be utilized for the prevention and treatment of endotoxin shock.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Benzamides / pharmacology*
  • Cell Nucleus / metabolism
  • Cell Proliferation / drug effects
  • Cells, Cultured
  • Cyclohexanones / pharmacology*
  • Interleukin-1beta / biosynthesis
  • Interleukin-6 / biosynthesis
  • Lipopolysaccharides / immunology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NF-kappa B / metabolism
  • RNA, Messenger / biosynthesis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Shock, Septic / drug therapy*
  • Shock, Septic / immunology*
  • Shock, Septic / prevention & control
  • Spleen / cytology
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / blood

Substances

  • Benzamides
  • Cyclohexanones
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • Tumor Necrosis Factor-alpha
  • dehydroxymethylepoxyquinomicin