The
neuroprotective effect of
maltol on oxidative damage in the brain of mice challenged with
kainic acid was examined. Male ICR mice, 6-8 weeks of age, were administered orally with
maltol (50 or 100 mg/kg) for 5 consecutive days. Thirty minutes after the final administration, the animals were challenged s.c. with
kainic acid (50 mg/kg), and neurobehavioral activities were monitored. In addition,
biomarkers of oxidative stress and neuronal loss in hippocampus for the biochemical and morphological evaluations were analyzed 2 days after the
kainic acid challenge. During 5-day treatment with
maltol, the
body weight gain was not significantly different from that of vehicle-treated control animals. Administration of
kainic acid alone induced severe epileptiform
seizures, causing a lethality of approximately 50%, and
injuries of pyramidals cells in hippocampus of mice survived the challenge.
Kainic acid exposure also resulted in marked decreases in total
glutathione level and
glutathione peroxidase activity, and an increase in
thiobarbituric acid-reactive substances (
TBARS) value in brain tissues. In comparison, coadministration with
maltol (100 mg/kg) remarkably attenuated the neurobehavioral signs and neuronal loss in hippocampus, leading to a decrease in mortality of animals to 12.5% (p < 0.05), although
maltol at a dose of 50 mg/kg failed to show any remarkable protection. In addition, the changes in
glutathione and
TBARS values and
glutathione peroxidase activity induced by
kainic acid were restored to control levels by pretreatment with
maltol (100 mg/kg). On the basis of these results,
maltol is suggested to be a functional agent to prevent the oxidative damage in the brain of mice.