Pathogenic molecular mechanisms in an animal model of fulminant hepatic
failure: rabbit hemorrhagic viral disease
S. Sánchez-Campos, J. M.
Culebras, M. Alvarez, J. González-Gallego, M. J. Tuñón
Journal of
Laboratory and Clinical Medicine:
144, 215-222, 2004
Abstract
This study was aimed to investigate whether molecular mechanisms participating
in the pathogenesis of fulminate hepatic failure are present in rabbits
experimentally infected with the rabbit hemorrhagic disease virus (RHDV). AST,
ALT and LDH activities, and bilirubin concentration increased significantly from
36h postinfection (pi). Animals also demonstrated significant decreases in
factor VII activity and the Fischer index activity and deterioration in
prothrombin time. Reduced glutathione concentration was significantly decreased
from 36h pi and there was a marked increase in the oxidised/reduced glutathione
ratio. Infected animals showed a progressive decrease in the liver activity of
the antioxidant enzyme superoxide dismutase. HGF and c-met expression was
progressively reduced from 24 h pi and no modification was detected in the mRNA
levels of TGFa.
These effects were accompanied by over-expression of TGFb1
at 24h and 36h pi and a significant increase in TNFa
mRNA levels at 36h pi. Experimental RHDV infection also induced a marked
activation of NF-kB
and a significant increase in iNOS mRNA levels from 24h pi. Data obtained from
this animal model confirm the presence of molecular mechanisms contributing to
lack of regeneration and apoptosis in fulminant hepatic failure.
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