Naloxone: a potent protective agent in ischemia – reperfusion – induced liver injury

Abstract

Hepatic ischemia/reperfusion-induced injury is accompanied
by free radical production, leading to endothelial cell
destruction, adhesion of neutrophils and plugging of the
hepatic sinusoids and thus to blood microcirculation flow
reduction. Naloxone is a known opioid antagonist that has
been shown to act by inhibiting the release of free radicals.
The purpose of this study is to clarify the changes in
hepatic microcirculation during liver ischemia and after
reperfusion in the rat and the potential beneficial effects
of Naloxone as pretreatment, in respect to microcirculation
and oxidative stress.
One hundred and forty male Wistar rats, allocated to
Naloxone [N] or Placebo [P] treatment, were subjected
to either 30min or 60min normothermic ischemia [70% of
total liver], followed by 60min reperfusion. Liver microcirculation
was assessed by laser-Doppler flowmetry at
baseline, at the end of the ischemia period [30min or
60min, respectively] and at the end of the reperfusion period,
while oxidative stress was assessed by means of MDA
at the same time periods.
Naloxone pretreatment seemed to protect liver parenchyma,
since MDA levels were significantly decreased in relation
to placebo treated rats, in both 30min ischemia/
60min reperfusion and 60min ischemia/60min reperfusion
groups. Similarly, Naloxone pretreatment was found to
significantly improve liver microcirculation in relation to
placebo treated rats, in both groups.
In conclusion, the results of this study indicate that
Naloxone pretreatment protects the liver from ischemia/
reperfusion hepatocellular injury.
Key words: Naloxone, ischemia/reperfusion injury, liver, laser-
Doppler flowmetry, malondialdehyde