Increased Endobiotic Fatty Acid Methyl Esters Following Exposure to Methanol

Abstract

Human exposure to methanol is likely to increase in the future due to its proposed use as an alternate automobile fuel. Since alcohols are known to esteri1 the fatty acids in the body and some of those esterifled esters are toxic, we studied the formation of fatty acid esters of methanol in Long-Evans male rats given a single oral dose of 3.5 g/kg body weight of methanol in saline. Animals given an equal volume of saline served as control. Three rats were euthanized at 1, 3, 6, 12, and 24 hr following the treatment. Fatty acid methyl esters, extracted from whole blood, liver, pancreas, and brown fat were separated by thin-layer chromatography and quantitated by gas chromatography (GC). Their identity was then confirmed by GC-mass spectrometry. Average levels as high as 596, 5293, 2239, 1106, 9665, 7728, 562, and 2792 μg/g (wet weight basis) of 14:0, 16:0, 16:1, 18:0, 18:1, 18:2, 18:3, and 20:4 fatty acid methyl esters, respectively, were found in the pancreas of methanol-treated rats. The average concentration of total fatty acid methyl esters was computed to be 4513, 29594, 22871, 18956, 17014, and 9702 μg/g in the pancreas compared to 1.9, 25.4, 36.8, 18.5, 18.9, and 14.2 μg/g in the liver at 0, 1, 3, 6, 12, and 24 hr, respectively, following methanol exposure. On dry lipid weight basis, the levels were significantly higher again in pancreas followed by brown fat and liver. In whole blood, only low levels of 16:0, 18:0, and 20:4 fatty acid methyl esters could be detected at all time points. The highest concentration of total fatty acid methyl esters in the pancreas, liver, and brown fat was detected at 1, 3, and 24 hr, respectively. Most of the fatty acid methyl esters found in the liver and pancreas decreased after 6 hr of methanol exposure. The fatty acid methyl esters of higher concentrations were 16:0 in the whole blood, 18:0, 18:1, 18:2, and 20:4 in liver, 18:1, and 18:2 in pancreas and 16:0, 18:1, and 18:2 in brown fat. These fatty acid methyl esters were also detected in the tissues of control rats indicating their endogenous formation. Significant increase in methylation of the fatty acids during methanol exposure, as found in this study, may serve as a defense mechanism for preventing available methanol from oxidative metabolism to render toxicity. However, the biological significance of these fatty acid methyl esters is yet to be understood.