DISSOCIATION OF MICROSOMAL OXYGEN REDUCTION AND LIPID PEROXIDATION WITH THE ELECTRON-ACCEPTORS, PARAQUAT AND MENADIONE

Paraquat, diquat and menadione, electron acceptors which interact with the microsomal electron transport chain, were used to investigate the relationship between microsomal lipid peroxidation and microsomal oxygen reduction. All three compounds stimulated hydrogen peroxide production and the rate of superoxide production by mouse liver microsomes. However, while paraquat and diquat stimulated microsomal lipid peroxidation (2-fold in liver microsomes and 6- to 10-fold in lung microsomes), menadione was a potent inhibitor. Superoxide dismutase and catalase had no effect on paraquat-stimulated lipid peroxidation. Diquat, at concentrations sufficient to stimulate Superoxide production, was unable to stimulate lipid peroxidation. Based on the above observations, a mechanism of paraquat- and diquat-initiated lipid peroxidation independent of superoxide and peroxide generation is proposed. The stimulatory effects of paraquat and diquat on lung microsomal lipid peroxidation are also discussed in relation to the lipid peroxidation hypothesis of paraquat lung toxicity. © 1979.