Methoxyacetaldehyde, an Intermediate Metabolite of 2-Methoxyethanol, IsImmunosuppressive in the Rat

摘要

2-Methoxyethanol (ME) is metabolized to 2-methoxyacetic acid (MAA) via theintermediate metabolite methoxyacetaldehyde (MAAD). In this study, the plaque-forming cell (PFC) response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was used to determine if MAAD is immunosuppressive in rats. Rats pretreated with the aldehyde dehydrogenase inhibitors disulfiram or cyanamide followed by oral dosing with ME resulted in suppressed PFC responses equivalent to the suppressed responses of rats dosed with ME alone. Rats pretreated with disulfiram and then dosed with 2.64 mmol/kg 2-methoxyethyl acetate (MEA), also resulted in suppressed PFC responses similar to that of MEA alone. In contrast, coadministration of the alcohol dehydrogenase inhibitor 4-methylpyrazole with ME or MEA blocked suppression of the PFC response following exposure to ME or MEA alone. Oral dosing with equimolar concentrations of ME, MAA, or MAAD resulted in equivalent suppression of the TNP-LPS PFC response. Rats exposed to either disulfiram or cyanamide and MAAD also resulted in suppression of the PFC response.