Effect of a perfluorochemical emulsion on the rat hepatic mixed function oxidase system.
The perfluorochemical components of synthetic oxygen transporting emulsions may persist in hepatic tissue. After a single 30% blood exchange with the perfluorochemical emulsion, Fluosol-DA 20%, the effects on the microsomal metabolism of 7-methoxycoumarin and 7-ethoxycoumarin were studied over a 9-week period. Fluosol-DA treated animals were compared with controls (sham) and hetastarch-treated controls. Changes in dealkylase activities were compared with induction by phenobarbitone and 3-methylcholanthrene. The liver to body weight ratio increased by 49% in Fluosol-DA-treated rats over the controls at 1 week and the microsomal protein was increased in the Fluosol-DA-treated rats after 4 and 9 weeks. Fluosol-DA treatment induced 7-methoxycoumarin demethylase with peak differences occurring at 1 week and a Vmax 75% greater than controls. Fluosol-DA was a more potent inducer of demethylase than phenobarbitone. In addition, 7-ethoxycoumarin de-ethylase was induced by Fluosol-DA with a peak induction at 4 weeks. The Vmax at 4 weeks in Fluosol-DA-treated rats was 122% greater than control. In this case, Fluosol-DA produced less induction in de-ethylase than 3-methylcholanthrene. These studies show that Fluosol-DA induces more than one form of cytochrome P450 and the effects resemble those of phenobarbitone more than those of 3-methylcholanthrene. Hetastarch, a plasma expander, did not affect liver weights, microsomal protein content, or the cytochrome P450 system.
Department of Pharmacal Sciences, School of Pharmacy, Auburn University, AL 36849.
W R
WR
Ravis
S
S
Ramakanth
D M
DM
Brzozowski
M E
ME
Hamrick
D015660:7-Alkoxycoumarin O-Dealkylase / Q000378:metabolism; D000818:Animals; D004338:Drug Combinations; D004655:Emulsions; D004790:Enzyme Induction / Q000187:drug effects; D005466:Fluorocarbons / Q000494:pharmacology*; D006895:Hydroxyethyl Starch Derivatives; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010951:Plasma Exchange; D010952:Plasma Substitutes; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D004338:Drug Combinations; D004655:Emulsions; D005466:Fluorocarbons; D006895:Hydroxyethyl Starch Derivatives; D010952:Plasma Substitutes; D011506:Proteins; C017323:glucose, glycerol, hydroxyethyl starch, perfluorodecalin, perfluorotripropylamine, pluronic F-68, salts, yolk phospholipids drug combination; D006899:Mixed Function Oxygenases; D015660:7-Alkoxycoumarin O-Dealkylase