Hyperbaric oxygen accelerates the neurotoxicity of 2,5-hexanedione.
The molecular pathogenesis of n-hexane neurotoxicity has been postulated to proceed as follows: The gamma-diketone metabolite, 2,5-hexanedione (HD), reacts with lysyl-amino groups on neurofilaments to form imines. The imines cyclize to form pyrroles. The pyrroles autoxidize, resulting in covalent protein-protein crosslinking within or between neurofilaments. A resultant impairment of neurofilament transport is proposed to lead to neurofilament-filled axonal swellings. This experiment was designed to test whether oxidation is a necessary pathogenetic step in vivo by comparing time of onset of paralysis of an HD treated group of rats to that of a group receiving HD plus oxygen under high pressure (OHP). The group of rats receiving the hyperbaric oxygen treatment reached the endpoint of hindlimb paralysis significantly sooner than the group receiving none. The fact that OHP does accelerate HD neuropathy points towards an oxidative step in the molecular pathogenesis of gamma-diketone neuropathy.
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001835:Body Weight / Q000187:drug effects; D004357:Drug Synergism; D006588:Hexanones / Q000633:toxicity*; D006931:Hyperbaric Oxygenation; D007382:Intermediate Filaments / Q000187:drug effects / Q000648:ultrastructure; D007659:Ketones / Q000633:toxicity*; D008297:Male; D009420:Nervous System / Q000187:drug effects*; D010243:Paralysis / Q000139:chemically induced; D051381:Rats; D011919:Rats, Inbred Strains
D006588:Hexanones; D007659:Ketones; C011269:2,5-hexanedione