Activation of
phospholipase A(2), degradation of membrane
phospholipids resulting in tissue accumulation of
arachidonic acid, and the activation of
cyclooxygenase that leads to the formation of
prostaglandin and
free radicals may occur after hypoxic-ischemic damage. The aim of this study was to investigate the effects of
indomethacin, a nonselective
cyclooxygenase inhibitor, on
caspase activity,
glutathione levels and lipid peroxidation in newborn rats with
hypoxic-ischemic encephalopathy. The effects of
indomethacin were evaluated by measuring
caspase-3 and
caspase-8 activities and
glutathione levels. Lipid peroxidation was evaluated by measuring concentrations of
malondialdehyde in rat brains. Seven-day-old rat pups with the Levine-Rice model of hypoxic-ischemic cerebral injury were randomly divided into three study groups. In the
indomethacin-treated group, rats were administered three doses of
indomethacin, at a dose of 2 mg/kg every 12 h.
Sham and the hypoxic-ischemic group of rats were given physiologic saline. The
sham group underwent all
surgical procedures except for arterial
ligation. After 72 hours, the rats were decapitated and brain tissues were evaluated.
Caspase-3 and
caspase-8 activities and
glutathione and
malondialdehyde levels were evaluated in all groups. There was an obvious decrease in
caspase-3 and
caspase-8 activities and depleted
glutathione levels were reversed in the
indomethacin-treated group compared to the hypoxic-
ischemia group (p<0.001). As
indomethacin was unable to prevent lipid peroxidation,
malondialdehyde concentrations increased to
ischemia-induced levels. In conclusion,
indomethacin administration after
hypoxic-ischemic encephalopathy injury has a
neuroprotective effect since it inhibits
caspase activity and reverses the depletion of
glutathione. However, it also aggravates lipid peroxidation-induced
ischemia.