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 exposur e to aldehydes, we studied glutathione (GSH) depletion by low-molecular-wei ght 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 correla tes with published values for the median lethal dose of the chemicals and w ith 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 eff ective in depleting GSH than were 2-alkenals (EC50, 2-180 mu mol/L), of whi ch acrolein was the most potent. Ability of the 2-alkenals to deplete GSH f ollows the second-order rate constant for adduct formation. Ability of n-al kanals to deplete GSH follows chain length. Within a homologous series of l ow-molecular-weight aldehydes, structure-activity relationships are useful for predicting the toxicity of the aldehydes in vitro and in vivo.