Evidence for Conversion of Methanol to Formaldehyde in Nonhuman Primate Brain.

Rongwei Zhai,Joshua Rizak,Na Zheng,Xintian Hu

doi:10.1155/2016/4598454

Abstract

Many studies have reported that methanol toxicity to primates is mainly associated with its metabolites, formaldehyde (FA) and formic acid. While methanol metabolism and toxicology have been best studied in peripheral organs, little study has focused on the brain and no study has reported experimental evidence that demonstrates transformation of methanol into FA in the primate brain. In this study, three rhesus macaques were given a single intracerebroventricular injection of methanol to investigate whether a metabolic process of methanol to FA occurs in nonhuman primate brain. Levels of FA in cerebrospinal fluid (CSF) were then assessed at different time points. A significant increase of FA levels was found at the 18th hour following a methanol injection. Moreover, the FA level returned to a normal physiological level at the 30th hour after the injection. These findings provide direct evidence that methanol is oxidized to FA in nonhuman primate brain and that a portion of the FA generated is released out of the brain cells. This study suggests that FA is produced from methanol metabolic processes in the nonhuman primate brain and that FA may play a significant role in methanol neurotoxicology.

Highlights

Methanol, a single carbon alcohol, is an important public health and environmental concern because it leads to metabolic acidosis, visual impairment, central nervous system dysfunction, neurodegenerative conditions, and death [1,2,3,4,5]
Formic acid has been found to be responsible for the metabolic acidosis witnessed in methanolintoxicated humans [12, 13] and nonhuman primates [14, 15] and the ocular toxicity observed in methanol-poisoned humans [12, 16] and nonhuman primates [17, 18]
In order to investigate elevated levels of intracranial FA following methanol injections, cerebrospinal fluid (CSF) samples from monkeys given a single methanol injection were taken before administration and at 3, 6, 12, 18, 24, and 30 hours after the injection

Summary

Introduction

A single carbon alcohol, is an important public health and environmental concern because it leads to metabolic acidosis, visual impairment, central nervous system dysfunction, neurodegenerative conditions, and death [1,2,3,4,5]. Methanol metabolism and mechanisms responsible for its toxic actions in primates have been extensively investigated in the periphery. The first step in the metabolic pathway is oxidation of methanol to formaldehyde (FA). A glutathionedependent formaldehyde dehydrogenase specific for FA catalyzes the conversion of FA to formic acid [1]. With respect to methanol toxicity, many studies have demonstrated that formic acid is primarily responsible for methanol’s toxicity. Formic acid has been found to be responsible for the metabolic acidosis witnessed in methanolintoxicated humans [12, 13] and nonhuman primates [14, 15] and the ocular toxicity observed in methanol-poisoned humans [12, 16] and nonhuman primates [17, 18]

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