Protective role of pentobarbital pretreatment for NMDA-R activated lipid peroxidation is derived from the synergistic effect on endogenous anti-oxidant in the hippocampus of rats.
We have attempted to explore the neuroprotective effectiveness of PBT by measuring anti-oxidant ability in the hippocampus of rats in a freely moving state. Anti-oxidant ability was examined utilizing the principle that blood-brain barrier-permeable nitroxide radicals (PCAM) injected i.p. lose their paramagnetism in an exponential decay correlated with anti-oxidant ability in the brain. The half-life of PCAM was used as the indicator of the hippocampal anti-oxidant ability. While the half-life was statistically prolonged when infused with 0.1mM NMDA without PBT, the half-life was almost the same as in the control when infused with NMDA under anesthesia with PBT. In addition, the half-life under only PBT anesthesia was the shortest of all the groups. Our findings, therefore, suggested that PBT anesthesia not only suppresses NMDA-R activated free radical generation but also synergistically enhances the increased basal endogenous anti-oxidant ability in the hippocampus.
Ueda
Yuto
Y
Section of Psychiatry, Department of Clinical Neuroscience, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan. usan@med.miyazaki-u.ac.jp
Doi
Taku
T
Nagatomo
Keiko
K
Nakajima
Akira
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D018690:Excitatory Amino Acid Agonists / Q000009:adverse effects / Q000378:metabolism; D005609:Free Radicals / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006993:Hypnotics and Sedatives / Q000494:pharmacology / Q000627:therapeutic use; D020925:Hypoxia-Ischemia, Brain / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D009498:Neurotoxins / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D000975:Antioxidants; D018690:Excitatory Amino Acid Agonists; D005609:Free Radicals; D006993:Hypnotics and Sedatives; D018696:Neuroprotective Agents; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D010424:Pentobarbital