Different contribution of rat liver microsomal pigments in the formation of superoxide anions and hydrogen peroxide during development

Abstract

Liver microsomes of adult rats produce, by an NADPH-dependent pathway, O 2 − radicals, as detected by the epinephrine cooxidation to adrenochrome (24.8 nmol/min/mg of protein). This production has also been measured during liver development (from 1 to 20 days after birth) and correlated to the enzyme content (NADPH-cytochrome c reductase, cytochrome b 5, and cytochrome P-450), with the aim of establishing the level at which Superoxide radicals are formed in the electron transport system. At 1 day the adrenochrome formation and the activity of NADPH-cytochrome c reductase are about 50 and 40% of those of the adult, respectively, whereas those of cytochromes b 5 and P-450 are approximately 10%. After 20 days of development cytochrome b 5 and the dehydrogenase reach the adult level, while cytochrome P-450 is about 80%. At this age O 2 − radicals have a 30% increment and reach only 60% of those of the adult; H 2O 2 production is also 60% and the N-demethylation of aminopyrine is only 30%. Thus, at birth the formation of O 2 − radicals is almost entirely dependent on the activity of the flavoprotein. The close correlation between the slight increase in the demethylase activity and adrenochrome formation from 1 to 20 days suggests that a portion of O 2 − radicals produced by the NADPH-dependent electron transfer is directly involved in the mixed function oxidation. Since about 50% of the radicals are formed at the flavoprotein level, these results indicate that in the adult liver the remaining amount may be generated at the level of cytochrome P-450.