title: Propofol exerts greater neuroprotection with disodium edetate than without it.
abstract: The main objective of this study, on mice, was to compare the neuroprotective effects of propofol with those of propofol plus disodium edetate (propofol EDTA). We also administered propofol EDTA (0.005% (w/v) EDTA) to mice intravenously, and measured the changes in zinc concentrations occurring after permanent middle cerebral artery occlusion. In the in vivo study, propofol EDTA displayed stronger neuroprotective effects than propofol alone. Furthermore, we examined the neuroprotective effects of EDTA administered alone, and found that EDTA Na significantly reduced the infarct volume. The number of terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling-positive cells in the ischemic penumbra was reduced more by propofol EDTA than by propofol alone. We performed in the in vitro study in five groups (aerobic, vehicle (control), propofol, EDTA, and propofol plus EDTA). Propofol and EDTA each protected PC12 cells against oxygen-glucose deprivation-induced cell damage, and the effect of propofol was increased by adding EDTA. Because the chelating action of EDTA was a potential causal mechanism, we examined the effect of propofol EDTA on intracerebral zinc homeostasis. When propofol EDTA was given intravenously 10 mins before cerebral ischemia, the zinc concentration decreased significantly in the cortical area, but not in the subcortex. In conclusion, (a) propofol provides neuroprotection against both in vivo and in vitro ischemic damage, and its effects are enhanced when EDTA is added; and (b) EDTA itself protects against ischemic neuronal damage, possibly, owing to its zinc-chelating action.
authors.affiliation: Department of Biofunctional Molecules, Gifu Pharmaceutical University, Gifu, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kotani
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Satoh
authors.forename: Hisamitsu
authors.initials: H
authors.lastname: Nagase
authors.forename: Masamitsu
authors.initials: M
authors.lastname: Shimazawa
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Toru
authors.initials: T
authors.lastname: Iwama
authors.forename: Hideaki
authors.initials: H
authors.lastname: Hara
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001562:Benzimidazoles; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology*; D004357:Drug Synergism; D004492:Edetic Acid / Q000494:pharmacology*; D005456:Fluorescent Dyes; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000473:pathology / Q000503:physiopathology; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology / Q000517:prevention & control; D008297:Male; D051379:Mice; D018696:Neuroprotective Agents; D020258:Neurotoxicity Syndromes / Q000473:pathology / Q000517:prevention & control*; D016716:PC12 Cells; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D015032:Zinc / Q000378:metabolism / Q000633:toxicity
chemical_list: D018686:Anesthetics, Intravenous; D001562:Benzimidazoles; D002614:Chelating Agents; D005456:Fluorescent Dyes; D018696:Neuroprotective Agents; D004492:Edetic Acid; D005947:Glucose; D015032:Zinc; C017807:bisbenzimide ethoxide trihydrochloride; D015742:Propofol