Evaluation of the neuroprotective action of WEB 1881 FU on hypoglycemia/hypoxia-induced neuronal damage using rat striatal slices.
Effect of WEB 1881 FU on hypoglycemia/hypoxia-induced brain damage in rats was evaluated and compared to findings obtained with idebenone. We used an in vitro model that facilitated the direct monitoring of dopamine release from striatal slices. The response to high K+ stimulation under perfusion of the slices with D-glucose-free Ringer solution (hypoglycemia) decreased at 40 min, and then practically disappeared. WEB 1881 FU at 10(-6) M or idebenone at 10(-6) M significantly protected against impairment of the striatal responses under the conditions of hypoglycemia. Hypoglycemic injury, evidenced by a remarkable neuron loss, necrosis and spongyosis was also ameliorated by these drugs. WEB 1881 FU at 10(-6) M had a protective action against the impairment of striatal responses evoked by NaCN (electron transport inhibitor at site 3) and oligomycin (inhibitor of mitochondrial ATP synthesis), but idebenone at 10(-6) M did not. In light of these observations, the possibility that WEB 1881 FU and idebenone exert neuroprotective actions against hypoglycemic/hypoxic brain injury by activating energy metabolism with different mechanisms from each other has to be considered.
Koizumi
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Kataoka
Y
Y
Shigematsu
K
K
Niwa
M
M
Ueki
S
S
D000818:Animals; D016227:Benzoquinones; D001927:Brain Diseases / Q000139:chemically induced / Q000503:physiopathology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects; D003486:Cyanides / Q000633:toxicity; D004298:Dopamine / Q000378:metabolism; D007003:Hypoglycemia / Q000503:physiopathology*; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009840:Oligomycins / Q000633:toxicity; D010276:Parasympatholytics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology; D011760:Pyrrolidinones / Q000494:pharmacology*; D011809:Quinones / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D014451:Ubiquinone / Q000031:analogs & derivatives
D016227:Benzoquinones; D003486:Cyanides; D009840:Oligomycins; D010276:Parasympatholytics; D011760:Pyrrolidinones; D011809:Quinones; D014451:Ubiquinone; C036619:idebenone; D011188:Potassium; C056640:nebracetam; D004298:Dopamine