Retracted: Trehalose: a biophysics approach to modulate the inflammatory response during endotoxic shock.
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.
Department of Clinical and Experimental Medicine and Pharmacology, University of Messina, Messina, Italy.
Letteria
L
Minutoli
Domenica
D
Altavilla
Alessandra
A
Bitto
Francesca
F
Polito
Ersilia
E
Bellocco
Giuseppina
G
Laganà
Tiziana
T
Fiumara
Salvatore
S
Magazù
Federica
F
Migliardo
Francesco Saverio
FS
Venuti
Francesco
F
Squadrito
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D055592:Biophysical Phenomena; D001703:Biophysics; D001794:Blood Pressure / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000097:blood; D004058:Diffusion; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000517:prevention & control; D020672:I-kappa B Proteins / Q000378:metabolism; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008107:Liver Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D008171:Lung Diseases / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008954:Models, Biological; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D009502:Neutrons; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012542:Scattering, Radiation; D012772:Shock, Septic / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013395:Sucrose / Q000494:pharmacology; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D014199:Trehalose / Q000494:pharmacology*; D014867:Water / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D020672:I-kappa B Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014867:Water; D000072000:NF-KappaB Inhibitor alpha; D009569:Nitric Oxide; D013395:Sucrose; D014199:Trehalose; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat