PMID- 18555988
OWN - NLM
STAT- MEDLINE
DCOM- 20081024
LR  - 20220410
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 589
IP  - 1-3
DP  - 2008 Jul 28
TI  - Trehalose: a biophysics approach to modulate the inflammatory response during 
      endotoxic shock.
PG  - 272-80
LID - 10.1016/j.ejphar.2008.04.005 [doi]
AB  - We evaluated the effects of trehalose against endotoxic shock, a condition in 
      which the loss of bio-membrane integrity plays a pivotal role. In addition we 
      performed a biophysics experiment by quasi elastic neutron scattering (QENS) 
      study, to investigate whether the membrane stability effect of trehalose might be 
      correlated with its high capability to switch-off the water diffusive dynamics 
      and, hence, the kinetic mechanisms of interaction. Endotoxic shock was induced in 
      male rats by a single injection of Salmonella enteritidis lipopolysaccharide 
      (LPS; 20 mg/kg/i.p.). Thirty minutes before and 2 h after LPS injection, the 
      animals were randomized to receive vehicle (1 ml/kg/i.p. 0.9%NaCl), sucrose (1 
      g/kg/i.p.) or trehalose (1 g/kg/i.p.). Mean arterial blood pressure, nuclear 
      factor-kappaB (NF-kappaB) binding activity, Ikappa-Balpha and toll-like 
      receptor-4 (TLR-4) activation were evaluated in both liver and lung. Plasmatic 
      tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), interleukin-6 
      (IL-6) and malondialdehyde (MDA) were also investigated. We studied liver injury 
      by means of blood alanine aminotransferase activity (ALT); inducible nitric oxide 
      synthase (iNOS) expression, myeloperoxidase (MPO) activity and tissue edema 
      evaluation. Lung injury was investigated by means of tissue monocyte 
      chemoattractant protein-1 (MCP-1) levels, MPO activity, iNOS expression and edema 
      formation. Trehalose reduced hypotension, NF-kappaB binding activity, 
      IkappaBalpha protein loss and TLR-4 activation. In addition trehalose reduced 
      TNF-alpha, IL-1, IL-6 and MDA levels. Trehalose also blunted liver and lung 
      injury. QENS measurements showed also that trehalose possesses a high "switching 
      off" capability. Sucrose did not modify endotoxic shock-induced sequelae. 
      Trehalose blocked the inflammatory cascade triggered by endotoxin shock, 
      stabilizing the bio-membranes and switching off the water diffusive dynamics.
FAU - Minutoli, Letteria
AU  - Minutoli L
AD  - Department of Clinical and Experimental Medicine and Pharmacology, University of 
      Messina, Messina, Italy.
FAU - Altavilla, Domenica
AU  - Altavilla D
FAU - Bitto, Alessandra
AU  - Bitto A
FAU - Polito, Francesca
AU  - Polito F
FAU - Bellocco, Ersilia
AU  - Bellocco E
FAU - Lagana, Giuseppina
AU  - Lagana G
FAU - Fiumara, Tiziana
AU  - Fiumara T
FAU - Magazu, Salvatore
AU  - Magazu S
FAU - Migliardo, Federica
AU  - Migliardo F
FAU - Venuti, Francesco Saverio
AU  - Venuti FS
FAU - Squadrito, Francesco
AU  - Squadrito F
LA  - eng
PT  - Journal Article
DEP - 20080412
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Cytokines)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Nfkbia protein, rat)
RN  - 0 (Tlr4 protein, rat)
RN  - 0 (Toll-Like Receptor 4)
RN  - 059QF0KO0R (Water)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 57-50-1 (Sucrose)
RN  - B8WCK70T7I (Trehalose)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, rat)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Biophysical Phenomena
MH  - Biophysics
MH  - Blood Pressure/drug effects
MH  - Cell Membrane/*drug effects/metabolism/pathology
MH  - Cytokines/blood
MH  - Diffusion
MH  - Disease Models, Animal
MH  - Edema/etiology/prevention & control
MH  - I-kappa B Proteins/metabolism
MH  - Lipopolysaccharides
MH  - Liver/*drug effects/enzymology/pathology
MH  - Liver Diseases/etiology/metabolism/physiopathology/*prevention & control
MH  - Lung/*drug effects/enzymology/pathology
MH  - Lung Diseases/etiology/metabolism/physiopathology/*prevention & control
MH  - Male
MH  - Models, Biological
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/metabolism
MH  - Neutrons
MH  - Nitric Oxide/metabolism
MH  - Nitric Oxide Synthase Type II/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Scattering, Radiation
MH  - Shock, Septic/chemically induced/*drug therapy/metabolism/physiopathology
MH  - Sucrose/pharmacology
MH  - Time Factors
MH  - Toll-Like Receptor 4/metabolism
MH  - Trehalose/*pharmacology
MH  - Water/metabolism
EDAT- 2008/06/17 09:00
MHDA- 2008/10/25 09:00
CRDT- 2008/06/17 09:00
PHST- 2007/07/11 00:00 [received]
PHST- 2008/03/21 00:00 [revised]
PHST- 2008/04/02 00:00 [accepted]
PHST- 2008/06/17 09:00 [pubmed]
PHST- 2008/10/25 09:00 [medline]
PHST- 2008/06/17 09:00 [entrez]
AID - S0014-2999(08)00399-3 [pii]
AID - 10.1016/j.ejphar.2008.04.005 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2008 Jul 28;589(1-3):272-80. doi: 10.1016/j.ejphar.2008.04.005. 
      Epub 2008 Apr 12.