Major role of soybean oil in preventing decrease in CYP4A1 mRNA content relative to PPARalpha mRNA down-regulation in infant rats.
Changes in the levels of CYP4A1, PPARalpha, and RXRalpha mRNA expression in the liver following overdose of fat-free or fat-containing total parenteral nutrition (TPN) were studied in 3-week-old male Sprague-Dawley rats. The rats were divided into three groups: group 1, oral diet; group 2, fat-free TPN; and group 3, TPN with 20% of calories from soybean oil emulsion. Levels of CYP4A1, PPARalpha, and RXRalpha mRNA in the fat-free TPN group were significantly lower than those in the other groups. Levels of CYP4A1 and PPARalpha mRNA were strongly correlated (r=0.849), and levels of CYP4A1 and RXRalpha mRNA were weakly correlated (r=0.618). This is the first report of a strong correlation between the levels of CYP4A1 and PPARalpha mRNA following overdose of fat-free or fat-containing TPN in infant rats. Our results also indicate that it is important to include fat in TPN regimens in order to prevent CYP4A1 mRNA down-regulation, which may be related to changes in PPARalpha mRNA levels in the liver.
Nishimura
Masuhiro
M
Division of Pharmacology, Drug Safety and Metabolism, Otsuka Pharmaceutical Factory Inc., 115 Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan. nisimums@otsukaj.co.jp
Yamauchi
Aiko
A
Yamaguchi
Mari
M
Kishimoto
Sanae
S
Ueda
Nobuhiko
N
Naito
Shinsaku
S
D000818:Animals; D001483:Base Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D017931:DNA Primers; D015536:Down-Regulation / Q000187:drug effects*; D008297:Male; D047493:PPAR alpha / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D047490:Retinoid X Receptor alpha / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013024:Soybean Oil / Q000494:pharmacology*
C465387:Cyp4a1protein, rat; D017931:DNA Primers; D047493:PPAR alpha; D012333:RNA, Messenger; D047490:Retinoid X Receptor alpha; D013024:Soybean Oil; D003577:Cytochrome P-450 Enzyme System; D000072470:Cytochrome P450 Family 4