Effects of fluoroquinolones on CYP4501A and 3A in male broilers.
The inhibitory effects of fluoroquinolones on the enzyme activity, protein levels and mRNA expression of liver cytochrome P450 (CYP) 1A and 3A were investigated in male broiler chicks. Enrofloxacin (20 mg/kg), sarafloxacin (8 mg/kg) and marbofloxacin (5.5 mg/kg) were administrated in drinking water for 7 consecutive days. A cocktail of the probe drugs caffeine and dapsone was used to determine CYP1A and 3A activity. Western blot analysis and real-time PCR were used to determine the effects on protein levels of CYP1A and 3A, and on CYP1A4, 1A5, 3A37 mRNA levels. Enrofloxacin increased the half-life of elimination for both caffeine and dapsone, and decreased expression of CYP1A and 3A protein. Marbofloxacin decreased the metabolism of caffeine and expression of CYP1A protein. However, no change in mRNA expression was observed for any treatment group. This suggested that high doses of enrofloxacin and marbofloxacin, but not sarafloxacin, inhibit CYP in chick liver raising the possibility of drug-drug interaction when using these compounds.
Zhang
Ling-Ling
LL
Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing 210095, China.
Zhang
Jun-Ren
JR
Guo
Kuan
K
Ji
Hui
H
Zhang
Yan
Y
Jiang
Shan-Xiang
SX
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D019540:Area Under Curve; D002110:Caffeine / Q000493:pharmacokinetics; D002645:Chickens / Q000378:metabolism*; D002939:Ciprofloxacin / Q000031:analogs & derivatives / Q000494:pharmacology; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D003622:Dapsone / Q000493:pharmacokinetics; D004347:Drug Interactions; D000077422:Enrofloxacin; D024841:Fluoroquinolones / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000502:physiology; D006207:Half-Life; D008099:Liver / Q000033:anatomy & histology; D008297:Male; D009929:Organ Size; D015430:Weight Gain / Q000187:drug effects
D000900:Anti-Bacterial Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D024841:Fluoroquinolones; D000077422:Enrofloxacin; D002110:Caffeine; D002939:Ciprofloxacin; D003622:Dapsone; C080260:marbofloxacin; D003577:Cytochrome P-450 Enzyme System; C047224:sarafloxacin