M. Oshita et al., PROTECTIVE EFFECT OF EBSELEN ON CONSTRICTIVE HEPATIC VASCULATURE - PREVENTION OF ALCOHOL-INDUCED EFFECTS ON PORTAL PRESSURE IN PERFUSED LIVERS, The Journal of pharmacology and experimental therapeutics, 271(1), 1994, pp. 20-24
The effect of an organoselenium compound, ebselen [2-phenyl-1,2-benzis
oselenazol-3-(2H)-one], on ethanol-induced liver damage through pertur
bation of microcirculation was investigated in perfused livers from fe
d rats. Infusion of ethanol at concentrations greater than or equal to
25 mM into the portal vein increased portal pressure in a concentrati
on-dependent manner. Release of lactate dehydrogenase (LDH) into the e
ffluent perfusate was minimal at 30 min; thereafter LDH release began
to increase gradually until the end of the experiment (60 min after th
e onset of ethanol infusion) and was dependent on ethanol concentratio
n. Simultaneous infusion of ebselen at a concentration of 10 or 30 mu
M with ethanol reduced significantly this ethanol-induced increase in
portal pressure by 50 to 75% (P < .05) and LDH release by 70% (P < .05
). When endothelin-1 or phenylephrine was infused into the liver, port
al pressure was increased, reaching maximal levels (50 +/- 17 and 46 /- 7 mm of H2O, respectively) and then decreasing gradually. Ebselen r
educed the maximal increase in portal pressure induced by endothelin-l
(18 +/- 2 mm of H2O) by 64% (P < .05). In addition, ebselen decreased
the maximal levels of portal pressure induced by phenylephrine (8 +/-
1 mm of H2O) by 83% (P < .05). These data indicate that ebselen has a
vasodilative effect on constriction of hepatic vasculature and dimini
shes ethanol-induced hepatic damage by offsetting ethanol-induced incr
ease in portal pressure. Thus, ebselen may prove useful for treatment
of alcoholic liver injury via improvement of microcirculatory disturba
nces.