Development and characterization of a nonprimate animal model of methanol-induced neurotoxicity

摘要

Humans and nonhuman primates are uniquely sensitive to the toxic effects of methanol. The toxic syndrome in these species is characterized by formic acidemia, metabolic acidosis and blindness or serious visual impairment. Nonprimate species are normally resistant to the accurulation of formate and associated metabolic and visual toxicity. We have developed a nonprimate mdel of methanol toxicity using rats in which formate oxidation has been selectively inhibited. Methanol-intoxicated rats developed formic acidemia, metabolic acidosis and visual toxicity analogous to the human methanol poisoning syndrome. Visual dysafunction was manifested as reductions in the flash evoked cortical potential and electroretinogram which occurred coincident with blood formate accumulation. Histopathologic studies revealed miitochondrial disruption and vaculolation in the retinal pigment epithelimum, photoreeceptor inner segments and optic nerve. The establishment of this nonprimate animal model of methanol intoxication will facilitate research into the mechanistic aspects of methoanol toxicity as well as the development and testing of treatments for human methanol poisoning. (Supported by The American Petroleum Institute and NIH grants ROl-ES06648 and P30-EYO193).