Induction and decline of hepatic cytochromes P4501A1 and 1A2 in rats exposed to hyperoxia are not paralleled by changes in glutathione S-transferase-alpha.
We investigated the effects of hyperoxia on the activities of hepatic ethoxyresorufin O-deethylase (EROD) (CYP1A1), methoxyresorufin O-demethylase (MROD) (CYP1A2), and glutathione transferase-alpha (GST-alpha), and the status of protein thiols (PSH) in male Sprague-Dawley rats. Twenty-four h of hyperoxia more than doubled EROD and MROD activities, which were increased 7.6- and 3.3-fold, respectively, after 48 h of hyperoxia. The increases in EROD and MROD activities were paralleled by enhanced CYP1A1/1A2 apoproteins contents, as detected by Western analysis. At 60 h of hyperoxia, by which time hyperoxic Sprague-Dawley rats display marked respiratory distress, pulmonary edema, and other markers of pulmonary dysfunction, the activities and levels of hepatic CYP1A1 and 1A2 had declined dramatically and returned to levels observed in air-breathing control animals. Hepatic activities of GST-alpha, as well as PSH status, were not altered significantly in the hyperoxic animals at any time point. The marked induction and subsequent decline of hepatic CYP1A1/1A2 activities in rats exposed to hyperoxia suggest that these enzymes may contribute to the mechanisms of injury and/or to adaptive responses to hyperoxic exposures in vivo.
Moorthy
B
B
Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA. bmoorthy@neomailbcm.pedi.bcm.tmc.edu
Nguyen
U T
UT
Gupta
S
S
Stewart
K D
KD
Welty
S E
SE
Smith
C V
CV
D000818:Animals; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis*; D019388:Cytochrome P-450 CYP1A2 / Q000096:biosynthesis*; D004790:Enzyme Induction; D005982:Glutathione Transferase / Q000378:metabolism*; D018496:Hyperoxia / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D005982:Glutathione Transferase