Infection (Actinobacillus pleuropneumoniae)-mediated suppression of oxidative hepatic drug metabolism and cytochrome P4503A mRNA levels in pigs.
The effect of Actinobacillus pleuropneumoniae infection, a well-characterized pig infection model, on both phase I (oxidative) and phase II (conjugative) microsomal enzyme activities was investigated in castrated male conventional pigs. A. pleuropneumoniae infection resulted after 24 hr in a significant suppression of 33% or more of all oxidative enzyme activities determined. After 40 hr, the activities were still suppressed, but did not differ from the results after 24 hr. On the contrary, all glucuronosyltransferase activities measured were not affected by A. pleuropneumoniae infection after both 24 and 40 hr. To elucidate further the mechanism of the suppression of oxidative enzyme activities, analysis of mRNA were conducted by dot-blot analysis using a human cytochrome P4503A4 cDNA probe. The results indicated that A. pleuropneumoniae infection suppressed oxidative enzyme activities. The reduction in cytochrome P4503A activity, specific for 6 beta-hydroxylation of testosterone is at a pretranslational level as measured by a decrease in the amount of mRNA.
Monshouwer
M
M
Department of Veterinary Basic Sciences, University of Utrecht, The Netherlands.
Witkamp
R F
RF
Nijmeijer
S M
SM
Van Leengoed
L A
LA
Verheijden
J H
JH
Van Miert
A S
AS
D000189:Actinobacillus Infections / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016977:Actinobacillus pleuropneumoniae; D000818:Animals; D019392:Cytochrome P-450 CYP2E1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D015342:DNA Probes; D014453:Glucuronosyltransferase / Q000378:metabolism; D015151:Immunoblotting; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000096:biosynthesis* / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000302:isolation & purification; D013552:Swine
D015342:DNA Probes; D012333:RNA, Messenger; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019392:Cytochrome P-450 CYP2E1; D014453:Glucuronosyltransferase