Eells J T
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
J Pharmacol Exp Ther. 1991 Apr;257(1):56-63.
Human methanol poisoning is characterized by formic acidemia, metabolic acidosis and blindness or serious visual impairment. Nonprimate species are ordinarily resistant to the accumulation of formate and the associated metabolic and visual toxicity. A nonprimate model of methanol-induced visual toxicity was developed using rats treated with subanesthetic concentrations of nitrous oxide to inhibit the oxidation of methanol's toxic metabolite, formic acid. Methanol-intoxicated rats developed formic acidemia, metabolic acidosis and visual toxicity within 36 hr of methanol administration analogous to the human methanol poisoning syndrome. Visual dysfunction was measured as reductions in the flash-evoked cortical potential and electroretinogram, which occurred coincident with blood formate accumulation. Alterations in the electroretinogram occurred at formate concentrations lower than those associated with other visual changes and provide functional evidence of direct retinal toxicity in methanol poisoning.
人类甲醇中毒的特征为甲酸血症、代谢性酸中毒以及失明或严重视力损害。非灵长类动物通常对甲酸盐的蓄积以及相关的代谢和视觉毒性具有抗性。通过用亚麻醉浓度的一氧化二氮处理大鼠以抑制甲醇有毒代谢物甲酸的氧化，建立了甲醇诱导的视觉毒性非灵长类动物模型。甲醇中毒的大鼠在给予甲醇后36小时内出现甲酸血症、代谢性酸中毒和视觉毒性，类似于人类甲醇中毒综合征。视觉功能障碍通过闪光诱发的皮层电位和视网膜电图的降低来衡量，这与血液中甲酸的蓄积同时发生。视网膜电图的改变发生在甲酸盐浓度低于与其他视觉变化相关的浓度时，并为甲醇中毒时视网膜直接毒性提供了功能证据。
