UNDERNUTRITION DURING HYPEROXIC EXPOSURE INDUCES CYP2E1 IN RAT-LIVER

Induction of cytochrome P450 2E1 (CYP2E1) has been shown to occur thro ugh two distinct mechanisms. The first is seen by treatment of rats wi th acetone, pyrazole, and 3-methyl-pyrazole, which induces CYP2E1 prot ein without affecting the mRNA level. The second is observed in starva tion, diabetes, and obesity, in which an increase of CYP2E1 protein is associated with an increase of the CYP2E1 mRNA. It has been reported by (Tindberg and Ingelman-Sundberg 1989) that hyperoxic exposure (95% O-2) induced a several-fold increase of CYP2E1 protein in both the liv er and lung of exposed rats without affecting the level of CYP2E1 mRNA . During the course of our previous study which demonstrated hyperoxia -induced specific pretranslational induction of CYP1A1/2 in the liver and CYP1A1 in the lung, we observed a progressive increase of hepatic CYP2E1 mRNA in animals of the hyperoxia group. Hyperoxia is accompanie d by some degree of starvation and our earlier experiments were conduc ted with rats of significantly greater body weight than those used by Tindberg and Ingelman-Sundberg (260 vs 150 g). Thus we reevaluated the changes of CYP2E1 in the current study with the use of food-restricte d control, and by utilizing rats of comparable weight (similar to 150 g) to that utilized by Tindberg and Ingelman-Sundberg. The results obt ained in the present study showed that there was a significant increas e in the levels of hepatic CYP2E1 mRNA, protein, and p-nitrophenol hyd roxylase activity in the food-restricted control group compared to the untreated controls. Rats from the hyperoxia group also demonstrated a similar increase of these three parameters in their livers but showed no significant difference compared with the results of the food-restr icted control group. Rats weighing similar to 260 g were also examined with similar food restriction and hyperoxia, and the results were ess entially similar to those obtained with the younger rats. The lungs of rats from food-restricted control and hyperoxia groups showed no incr ease of any of the CYP2E1 parameters. The results obtained in the curr ent study, therefore, indicate that hyperoxia has no effect on CYPZE1 expression in both the liver and lung. Increased CYP2E1 mRNA, protein, and p-nitrophenol hydroxylase activity seen in the liver of rats? but not in the lungs, are consistent with the notion that undernutrition during hyperoxia is the underlying mechanism for this induction.