Effects of ionophores on liver CYP1A and 3A in male broilers.
The effects of ionophore antibiotics on the enzyme activity, protein and mRNA expression levels of cytochrome P450 (CYP) isoenzymes were investigated in liver from male Arbor Acres (AA) broiler chicks. Monensin, salinomycin and maduramycin at the dosage of 120, 60, and 5 mg/kg were administered in feed for 14 days. CYP1A and CYP3A activities were quantitated using cocktail probe drugs and a high performance liquid chromatographic (HPLC) assay at the 15th day; the protein expressions of CYP1A and CYP3A were detected by Western blot. CYP1A4, CYP1A5 and CYP3A37 mRNA levels were detected by real-time polymerase chain reaction (real-time PCR). Monensin, salinomycin and maduramycin had no effect on caffeine metabolism, protein expression and mRNA expression, but did induce dapsone metabolism, increasing CYP3A protein expression. However, there was no change in CYP3A37 mRNA expression as compared with the control group. It is suggested that ionophore antibiotics may have an induction effect on CYP3A expression and enzyme activity and that such effect might be related to the posttranscriptional regulation of its protein expression. Consideration of the enhanced metabolism of other drugs used simultaneously with ionophores is therefore recommended.
College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
L L
LL
Zhang
J R
JR
Zhang
Z G
ZG
Yu
J
J
Zhao
F
F
Mo
S X
SX
Jiang
D000818:Animals; D015153:Blotting, Western / Q000662:veterinary; D002110:Caffeine / Q000494:pharmacology; D002645:Chickens; D002851:Chromatography, High Pressure Liquid / Q000662:veterinary; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A / Q000096:biosynthesis / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D003622:Dapsone / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D007476:Ionophores / Q000494:pharmacology*; D007783:Lactones / Q000494:pharmacology; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008985:Monensin / Q000494:pharmacology; D011714:Pyrans / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D000095662:Polyether Polyketides
D002110:Caffeine; D019363:Cytochrome P-450 CYP1A1; D051544:Cytochrome P-450 CYP3A; D003622:Dapsone; D007476:Ionophores; D007783:Lactones; D008985:Monensin; D011714:Pyrans; D012333:RNA, Messenger; C018091:maduramicin; C010327:salinomycin; D000095662:Polyether Polyketides