Neuroprotective effect of maltol against oxidative stress in brain of mice challenged with kainic acid.
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.
Kim
Yun-Bae
YB
College of Veterinary Medicine, Research Institute of Veterinary Medicine, Chungbuk National University, Cheongju 361-763, South Korea.
Oh
Sang Hee
SH
Sok
Dai-Eun
DE
Kim
Mee Ree
MR
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000187:drug effects / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D007608:Kainic Acid / Q000494:pharmacology*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D011753:Pyrones / Q000494:pharmacology*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis
D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D011753:Pyrones; D017392:Thiobarbituric Acid Reactive Substances; C008316:maltol; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione; D007608:Kainic Acid