چکیده (انگلیسی):

Alterations in liver vascular tone play an important role in chronic liver disease. The hepatic
stellate cell (HSC) and mediators such as nitric oxide (NO) and hydrogen sulfide (H2S)
have been implicated in regulation of vascular tone and intra-hepatic pressure. Though
these have been studied in chronic liver damage, changes in response to acute liver injury
induced by hepatotoxins such as dimethyl nitrosamine are not well understood. Liver injury
was induced in mice by a single intra-peritoneal injection of dimethylnitrosamine (DMN),
following which animals were sacrificed at 24, 48 and 72 h. Changes in vascular mediators
such as NO and H2S as well as stellate cell activation was then examined. It was found
that a single low dose of DMN in mice is sufficient to induce activation of hepatic stellate
cells within 24 h, accompanied by oxidative stress, compromised metabolism of H2S and
decreased levels of the von Willebrand factor (vWF) cleaving protease; a disintegrin and
metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13), which
functions in intravascular thrombosis. A suppression of hepatic NO levels is also initiated at
this time point, which progresses further and is sustained up to 72 h, at which point the HSC
activation is still present. Compromised levels of ADAMTS13 and H2S metabolism however,
begin to recover by 48 h and are almost similar to control by 72 h. In conclusion, these data
suggest that even moderate acute insults in the liver can have far reaching consequences
on a number of mediators of vascular flow in the liver.