Distribution and oxidation of malondialdehyde in mice

The metabolism of melondialdehyde (MDA) by male and female Swiss mice was investigated. Distribution of an i.p. dose of MDA is rapid and uniform throughout the body. Conversion of ¹⁴C-labeled MDA to CO₂ is complete 4 hours after an i.p. dose of 5 μmol to 200 μmol with no signs of short term toxicity. The yields of CO₂ from 1-¹⁴C]-β-alanine, 3-¹⁴C]-β-alanine, 1-¹⁴C]-sodium acetate, and 2-¹⁴C]-sodium acetate were also determined. Comparison of the yields of CO₂ from this series of compounds suggests the intermediacy of malonic semialdehyde in the metabolism of MDA. High doses (600 μmol) of β-alanine or acetate given prior to ¹⁴C-MDA reduced the yield of ¹⁴CO₂. Ethanol and disulfiram were both inhibitors of MDA metabolism, indicating the involvement of aldehyde dehydrogenase in the oxidation of MDA.These data demonstrate the ability of animal tissues to rapidly remove exogeneously administered MDA. They also have implications with respect to the possible pathological consequences of MDA generation.