Cumene hydroperoxide-generated spectral interactions of piperonyl butoxide and other synergists with microsomes from mammals and insects

Piperonyl butoxide-dependent formation of type III difference spectra and the resulting inhibition of carbon monoxide binding by microsomal cytochrome P-450 were investigated using a cumene hydroperoxide-supplemented reaction medium. Cumene hydroperoxide is capable of supporting the formation of type III spectra with piperonyl butoxide and microsomes from several different species. NADPH is not required in the presence of cumene hydroperoxide. Similarities and differences between NADPH- and cumene hydroperoxide-mediated reactions were noted. Comparative studies indicated that, as in mammals, insect microsomal cytochrome P-450 also possesses peroxidase activity. In addition to piperonyl butoxide, other methylenedioxyphenyl compounds such as sulfoxide, n-propyl isome, and sesamol also give rise to a similar spectral response in either NADPH- or cumene hydroperoxide-supplemented reaction media. The significance of the cumene hydroperoxide-dependent reaction in elucidating the mechanism of synergistic action of methylenedioxyphenyl compounds is discussed.