01226-A: Evaluation of Multidrug Resistance Genes in Primary Canine Lymphoma Cells Exposed to Enrofloxacin and Prednisolone

Grant Status: Closed

Grant Amount: $7,139.1
Dr. Annette N. Smith, DVM, Auburn University
February 1, 2009 - January 31, 2010
Sponsor(s): American Foxhound Club
Breed(s): -All Dogs
Research Program Area: Treatment

Project Summary

Enrofloxacin is a commonly used antibiotic in veterinary medicine for selected bacterial infections. Selected fluoroquinolones and prednisone are known substrates for P-glycoprotein. As such, drugs can compete for and inhibit or induce P-glycoprotein. To date, enrofloxacin has not been evaluated as a possible substrate for MDR1. Prednisolone is a known substrate of MDR1. However, the impact of either drug on canine P-glycoprotein is unknown. Additionally, it is unclear as to how long the exposure must be in order to induce the MDR1 gene. The goal of this research was to evaluate the expression of a drug resistance gene, MDR1, in response to exposure to either an antibiotic, enrofloxacin, or a corticosteroid, prednisolone, in canine lymphoma cells. The researchers evaluated the expression of MDR1 at varying lengths of time of prednisolone exposure. Based on this research, it appears the shortening of survival time in dogs pre-treated with prednisone prior to initiating chemotherapy for lymphoma may not be related to the upregulation of the multi-drug resistance gene that was evaluated. The antibiotic, enrofloxacin, also appears to lack the ability to upregulate this gene with two weeks of drug exposure in the cell lines studied. Other mechanisms for the shortened survival time should be evaluated.

Publication(s)

Brugmann, BL, Smith AN, Price HL, Boothe DM, Higginbotham ML, Whitley EM, Smith BF, Behrend EN. In vitro evaluation of ABCB1 after exposure to prednisolone and enrofloxacin in two canine lymphoid cell lines and a canine mammary cell line. In preparation for submission to Veterinary and Comparative Oncology within the next 6 months.

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