Effects of fluoroquinolone treatment on MDR1 and MRP2 mRNA expression in Escherichia coli-infected chickens.
Current knowledge about the expression of ABC transport proteins suggests that their expression is regulated by a variety of factors, including pathological conditions, and in particular inflammatory reactions to infection. As ABC transporters are major determinants of absorption, distribution and excretion of many antimicrobials, modulation of their activity may result in increased or decreased tissue levels of drugs, affecting the efficacy of treatment. As fluoroquinolones have been identified as modulators and substrates of a number of drug transporters, we evaluated the effect of danofloxacin mesylate and enrofloxacin treatment on the levels of expression of MDR1 and MRP2 mRNAs in the intestines and livers of broilers with experimentally induced colibacillosis. MDR1 mRNA expression was significantly decreased in infected animals and was partly restored over 5 days of treatment with orally administered danofloxacin mesylate or enrofloxacin. Changes in the level of expression of MRP2 mRNA were less prominent. The study suggests that the treatment of colibacillosis with fluoroquinolones, which resulted in a significant clinical improvement of the animals, also restored the expression of drug transporters. This is of clinical importance as these ABC transporters significantly contribute to the functionality of important biological barriers, protecting the bird and specific tissues from pathogens and bacterial toxins.
Haritova
Aneliya Milanova
AM
Department of Pharmacology, Veterinary Physiology and Physiological Chemistry, Faculty of Veterinary Medicine, Trakia University, Bulgaria.
Rusenova
Nikolina Velizarova
NV
Rusenov
Anton Georgiev
AG
Schrickx
Jan
J
Lashev
Lubomir Dimitrov
LD
Fink-Gremmels
Johanna
J
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D002645:Chickens; D000077422:Enrofloxacin; D004927:Escherichia coli Infections / Q000378:metabolism / Q000662:veterinary*; D005260:Female; D024841:Fluoroquinolones / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D011201:Poultry Diseases / Q000378:metabolism* / Q000382:microbiology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D018528:ATP-Binding Cassette Transporters; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D012333:RNA, Messenger; C068581:danofloxacin; D000077422:Enrofloxacin