Stimulation of microsomal lipid peroxidation by iron and cysteine. Characterization and the role of free radicals.

The stimulation of microsomal lipid peroxidation by FeSO4 and cysteine has been investigated. Although both FeSO4 and cysteine alone promoted an increase in malonaldehyde production, when these agents were added together to microsomes the resultant level of malonaldehyde was greater than the sum of the amounts formed by these pro-oxidants when acting individually. A further indication of an interaction between FeSO4 and cysteine was shown by the inhibitory action of chelating agents. Stimulation of peroxidation was shown to be independent of microsomal protein, including cytochrome P-450. The system has been characterized for the effects of cysteine, Fe2+ and O2 concentrations, pH, temperature and antioxidants. The results indicate that the high level of peroxidation attained with this system, its non-enzymic character and the involvement of hydroxyl radicals make it particularly useful for the investigation of the action of antioxidants. Furthermore it may also be a model of way in which decompartmentalized, delocalized or 'free' iron initiates peroxidation in vivo.