Endothelin antagonists are being investigated to prevent neuronal loss after
cerebral ischemia.
Acetaminophen has been tried in
stroke patients to produce
hypothermia so that injury following
cerebral ischemia can be reduced. The aim of this study was to assess the effect of
BQ123, an
endothelin-A receptor antagonist, alone and in combination with
acetaminophen on neurological outcome, oxidative stress and
infarct volume in rats subjected to focal
ischemia by occlusion of the middle cerebral artery. In normal rats,
acetaminophen decreased, while
BQ123 did not produce any change in body temperature, but rats treated with
BQ123 and
acetaminophen produced a significantly greater (41%) hypothermic response compared to
acetaminophen group. In rats subjected to
middle cerebral artery occlusion,
neurologic deficit was observed;
acetaminophen alone did not improve, but
BQ123 alone and in combination with
acetaminophen produced a significant improvement in neurological deficit. The level of
malondialdehyde (MDA) increased and
reduced glutathione (GSH) decreased in the brain following
ischemia;
acetaminophen did not but
BQ123 alone and in combination with
acetaminophen decreased MDA and increased GSH levels in ischemic rats.
Cerebral ischemia produced significant
infarction, the
infarct volume decreased in response to
BQ123 and its combination with
acetaminophen. The
infarct volume, MDA level and neurological deficit in ischemic rats significantly improved in rats treated with both
BQ123 and
acetaminophen compared to
BQ123 alone. The results demonstrate that a combination of
acetaminophen and
BQ123 is more effective in reducing the neuronal damage following
cerebral ischemia, and this combination may be worth investigating in
stroke patients.