MIXED-FUNCTION OXIDASE ACTIVITY IN SEPSIS

Hepatic dysfunction is a major contributor to death in multiple organ system failure. To evaluate whether this dysfunction increases with th e length of sepsis, we studied the effect of fulminant CLP peritonitis with hyperoxia on mixed-function oxidase-MFO (cytochrome P450 content and activity) and lipid peroxidation in rat livers, Livers were harve sted at 18, 21, 24, and 27 hr, homogenized, and microsomal fractions p repared. Cytochrome P450 concentration was determined by assay and P45 0 activity was determined by the metabolism of ethoxyresorufin and eth oxycoumarin. Lipid peroxidation was estimated by measuring malondialde hyde content. Septic rats showed decreases in P450 levels and activity , which worsened with duration of sepsis. These decreases were partial ly lessened by hyperoxia, Although there was a trend toward increased lipid peroxidation, this effect was not statistically significant, Thi s study suggests that while MFO content and activity decrease with sep sis, these decreases do not appear to be related to the production of oxygen-derived free radicals. Furthermore, hyperoxia actually appears to have a protective role in this instance. (C) 1995 Academic Press, I nc.