HEAD-INJURY AND CYTOCHROME-P-450 ENZYMES - DIFFERENTIAL EFFECT ON MESSENGER-RNA AND PROTEIN EXPRESSION IN THE FISCHER-344 RAT

Head trauma produces debilitating injuries that affect millions of peo ple each year. Such injuries lead to a cascade of physiologic sequela resulting in a hypercatabolic/hypermetabolic state. Current informatio n describing changes in hepatic drug metabolism as a result of head tr auma is limited. In this study, the effect of craniotomy and craniotom y plus cerebral percussive injury (impact) were investigated and compa red with anesthesia control. Steady-state mRNA levels for CYP2C11 and CYP3A were suppressed to 50% of control values 24 hr following injury for the impact treatments. Craniotomy treatments also demonstrated a 5 0% decline in steady-state levels of mRNA for CYP3A 24 hr following in jury. However, Western blot analysis of the CYP3A enzyme revealed no c hange at 6, 24, or 48 hr following injury. In addition, activities for 2alpha- and 6beta-testosterone hydroxylase did not differ from contro l values at any time point. Spectral analysis of total P-450 demonstra ted a very small decline of 15% for the impact treatment 48 hr followi ng injury. Total cytochrome P-450 content did not differ from control values at any other time point. Head injury produces a profound declin e in steady-state mRNA concentrations for CYP2C11 and CYP3A that do no t translate into altered protein expression.