Makar A B, Tephly T R, Sahin G, Osweiler G
University of Osteopathic Medicine and Health Sciences, Des Moines, Iowa 50312.
Toxicol Appl Pharmacol. 1990 Sep 1;105(2):315-20. doi: 10.1016/0041-008x(90)90192-w.
Formate generated from methanol metabolism in vivo is the chemical entity responsible for the development of the methanol toxicity syndrome in the monkey. Compared to rats, monkeys are in a state of folate deficiency. This leads to a decreased ability to dispose of formate generated leading to its accumulation and the subsequent development of the classic symptoms of methanol toxicity. Rats possess a more efficient folate system; therefore, they metabolize formate very readily and do not exhibit methanol toxicity symptoms. In this report, the hepatic folate content and the ability to handle a formate "load" were evaluated in another animal species, the pig. The results obtained indicate that the pig, compared to all other species studied, has extremely low levels of folates and very low levels of a key enzyme in the folate pathway, namely 10-formyl H4folate dehydrogenase. Also the pig's ability to dispose of formate was extremely limited and slower than that observed in rats or monkeys. These results suggest that the pig may be a suitable animal model for studying formate metabolism and possibly methanol toxicity.
体内甲醇代谢产生的甲酸是导致猴子出现甲醇中毒综合征的化学物质。与大鼠相比,猴子处于叶酸缺乏状态。这导致处理产生的甲酸的能力下降,从而导致甲酸积累以及随后出现甲醇中毒的典型症状。大鼠拥有更高效的叶酸系统;因此,它们很容易代谢甲酸,不会出现甲醇中毒症状。在本报告中,对另一种动物——猪的肝脏叶酸含量和处理甲酸“负荷”的能力进行了评估。获得的结果表明,与所有其他研究的物种相比,猪的叶酸水平极低,叶酸途径中的一种关键酶——10-甲酰四氢叶酸脱氢酶的水平也非常低。此外,猪处理甲酸的能力极其有限,且比在大鼠或猴子中观察到的要慢。这些结果表明,猪可能是研究甲酸代谢以及可能的甲醇毒性的合适动物模型。