In vitro stimulation by paraquat of reactive oxygen-mediated lipid peroxidation in rat lung microsomes

Paraquat significantly stimulated lipid peroxidation in rat lung microsomes without the addition of exogenous iron. The ability of paraquat to stimulate this lipid peroxidation was dependent on the presence of adequate reducing equivalents (NADPH), aerobic conditions, and the duration of incubation, viz. optimal in vitro conditions. Even greater paraquat-mediated lipid peroxidation was observed if incubations were conducted under O₂ or if vitamin E-deficient microsomes were utilized, factors which have previously been reported to increase the in vivo pulnonary toxicity of paraquat. Superoxide dismutase (3 μg/ml) significantly inhibited paraquat-stimulated lipid peroxidation in rat lung microsomes (73%), demonstrating a pivotal role for superoxide in this process. Thus, the redox cycling of paraquat and accompanying reactive oxygen generation was capable of mediating lipid peroxidation not only in mouse lung and rat liver microsomes but also in rat lung microsomes.