Deterioration of axonal membranes induced by phenolic pro-oxidants. Roles of superoxide radicals and hydrogen peroxide.
The susceptibility of axons to oxidative free radicals generated by pro-oxidant neurotoxins and related compounds was tested by applying the reagents to the disheathed ventral nerve trunk of the crayfish. Electrophysiological characteristics of the axons, including spike amplitude and rise time, were recorded, using intracellular glass microelectrodes. L-Dopa, or L-dopa in the presence of copper-(bis)-histidine (Cu-his), did not change significantly the electrophysiological characteristics of the axon. A 20 mM concentration of 6-hydroxydopamine (6-OHDA), 20 mM 6-OHDA in an anaerobic environment, and 20 mM 6-OHDA with inactivated catalase-SOD accelerated the rate of decline of the spike amplitude with time to 5-8 times the control rate. Simultaneously, parallel increases in rise time and spike duration were observed, consistent with partial depolarization of the resting membrane presumably resulting from increased permeability. Catalase, superoxide dismutase (SOD), or a mixture of catalase and SOD all afforded partial protection, catalase having the least protective effect, and catalase + SOD the greatest. In contrast, 20 mM H2O2, 2 mM H2O2, or Cu-his alone did not significantly accelerate deterioration of the axon. Most of the damage results from the interaction of H2O2 with O-2, rather than from the direct action of either species. p-Hydroxyphenylpyruvate (pHPP) in the presence of Cu-his induced a similar accelerated deterioration of the axon to 4.2 times the control rate. Catalase plus SOD partially protected against this effect, but either enzyme alone was not significantly protective.
D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D002374:Catalase / Q000494:pharmacology; D004553:Electric Conductivity / Q000187:drug effects; D004558:Electric Stimulation; D006861:Hydrogen Peroxide / Q000378:metabolism*; D006892:Hydroxydopamines / Q000494:pharmacology*; D007980:Levodopa / Q000494:pharmacology*; D009410:Nerve Degeneration / Q000187:drug effects*; D016627:Oxidopamine; D013482:Superoxide Dismutase / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*
D006892:Hydroxydopamines; D013481:Superoxides; D007980:Levodopa; D016627:Oxidopamine; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase