Glutathione depletion in lung cells by low-molecular-weight aldehydes

Use of oxygenates in gasoline in the United States may increase atmospheric levels of aldehydes. To assist in health assessments of inhalation exposure to aldehydes, we studied glutathione (GSH) depletion by low-molecular-weight n-alkanals and 2-alkenals, ubiquitous air pollutants, in adult rat lung (ARL) cells by laser cytometry. For each homologous series, the effective aldehyde concentration that depleted GSH by 50% (EC50) in ARL cells correlates with published values for the median lethal dose of the chemicals and with Hammett/Taft electronic parameters, sigma* for n-alkanals and sigma(+)p for 2-alkenals. n-Alkanals (EC50, 110-400 mmol/L) were 1000 times less effective in depleting GSH than were 2-alkenals (EC50, 2-180 micromol/L), of which acrolein was the most potent. Ability of the 2-alkenals to deplete GSH follows the second-order rate constant for adduct formation. Ability of n-alkanals to deplete GSH follows chain length. Within a homologous series of low-molecular-weight aldehydes, structure-activity relationships are useful for predicting the toxicity of the aldehydes in vitro and in vivo.