RT info:eu-repo/semantics/preprint
T1 Melatonin inhibits the sphingosine kinase 1/sphingosine-1-phosphate signaling pathway in rabbits with fulminant hepatitis of viral origin
A1 Crespo, Irene
A1 San-Miguel, Beatriz
A1 Sánchez, Diana I.
A1 González-Fernández, Bárbara
A1 Álvarez, Marcelino
A1 González Gallego, Javier
A1 Tuñón González, María Jesús
A2 Otros
K1 Medicina. Salud
K1 Liver
K1 Sphingosine kinase 1
K1 Sphingosine-1-phosphate
K1 Acute liver failure
K1 Melatonin
AB The sphingosine kinase (SphK)1/sphingosine-1-phosphate (S1P) pathway is involved inmultiple biological processes, including liver diseases. This study investigate whether modulationof the SphK1/S1P system associates to the beneficial effects of melatonin in an animal model ofacute liver failure (ALF) induced by the rabbit hemorrhagic disease virus (RHDV). Rabbits wereexperimentally infected with 2x104 hemagglutination units of a RHDV isolate and received 20mg/kg of melatonin at 0 hr, 12 hr and 24 hr postinfection. Liver mRNA levels, proteinconcentration and immunohistochemical labelling for SphK1 increased in RHDV-infected rabbits.S1P production and protein expression of the S1PR1 receptor were significantly elevated followingRHDV infection. These effects were significantly reduced by melatonin. Rabbits also exhibitedincreased expression of toll-like receptor (TLR)4, tumor necrosis factor alpha (TNF-α), interleukin(IL)-6, nuclear factor-kappa B (NF-κB) p50 and p65 subunits and phosphorylated inhibitor of kappaB (IκB)α. Melatonin administration significantly inhibited those changes and induced a decreasedimmunoreactivity for RHDV viral VP60 antigen in the liver. Results obtained indicate that theSphK1/S1P system activates in parallel to viral replication and the inflammatory process induced bythe virus. Inhibition of the lipid signaling pathway by the indole reveals novel molecular pathwaysthat may account for the protective effect of melatonin in this animal model of ALF, and supportsthe potential of melatonin as an antiviral agent
PB Wiley
YR 2016
FD 2016-12-19
LK http://hdl.handle.net/10612/5689
UL http://hdl.handle.net/10612/5689
NO Journal of Pineal Research, 2016
NO 25 p.
DS BULERIA. Repositorio Institucional de la Universidad de León
RD 21-may-2024