Hypoxic and posthypoxic neuronal injury in hippocampal cell culture: attenuation by lipophylic antioxidant U-18 and superoxide dismutase.
The neuroprotective effects of synthesized lipophylic antioxidant from hindered phenol class (U-18) and hydrophylic antioxidative enzyme superoxide dismutase (SOD) were tested on long-term mouse hippocampal cell cultures exposed to hypoxia/reoxygenation. The application of U-18 to the cultures during 6-8 hr hypoxia followed by 16-18 hr reoxygenation in the absence of antioxidant significantly reduced neuronal death. Thus, lipophylic free radical scavenger may exert a delayed neuroprotective effect, probably owing to persistent incorporation into phospholipid membranes and prevention of their lipid peroxidation by means of prolonged intramembranous free radical quenching. On the other hand, the exposure of the cultures to U-18 during 15 hr hypoxia without subsequent reoxygenation also led to significant reduction of neuronal death compared with that observed without antioxidant. These findings suggest that free radical neuronal damage may occur under conditions of prolonged restricted oxygen access to the neurons. The hypoxic/posthypoxic neuronal injury significantly decreased in the cultures exposed to hydrophylic cytoplasmic enzyme SOD (300 U/ml). The neuroprotective effects of both lipophylic U-18 and hydrophylic SOD on the cultures exposed to hypoxia/reoxygenation might reflect the damaging free radical overproduction in different morphofunctional compartments of the nerve cell.
Khaspekov
L G
LG
Brain Research Institute, Russian Academy of Medical Sciences.
Lyzhin
A A
AA
Victorov
I V
IV
Dupin
A M
AM
Erin
A N
AN
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D010636:Phenols / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000494:pharmacology*
D000975:Antioxidants; D010636:Phenols; C096234:U-18; D015763:2-Amino-5-phosphonovalerate; D013482:Superoxide Dismutase