Volume 59 (2009) Issue: 2009 No#5-6

Evaluation of flunixin meglumine genotoxicity using in vitro and in vivo/in vitro micronucleus test

Author(s): Aydin SA, Üstüner Keles O

Keywords:cytochalasin-B, flunixin meglumine, micronucleus, mice, peripheral lymphocytes

The aim of this study was to investigate the genotoxic effects of flunixin meglumine on mice peripheral lymphocytes by in vitro and in vivo/invitro cytokinesis block micronucleus tests (CBMN). Flunixin meglumine was used at concentrations of 25, 50 and 100 μg/mL for the in vitro assay and 50, 75 and 100 mg/kg for the in vivo/in vitro assay. Mice were treated intraperitonally twice with a 24 h interval and sacrificed 6 h after the last dose. Cardiac blood was taken and added to the cultures for the in vivo/in vitro test. 21 h after the addition of the test compund for the in vitro test, and after the initiation of incubation for in vivo/in vitro test cytokinesis was blocked with the addition of cytochalasin-B and 20 h later the cultures were harvested. In both test systems, a negative and a positive control mitomycin C (MMC) were also included. The micronucleated binuclear cell (MNBN) frequencies increased after both treatments, however, the differences between the treated cells and the control groups were found to be statistically significant only for the in vitro treatment. The increase was in a dosedependent manner, significant elevations of MNBN cell (p<0.05 and p<0.001) were observed at concentrations 50 and 100 μg/mL respectively. In addition reduction in cytokinesis-block proliferation index (CBPI) was observed in both treatments, indicating cytotoxicity of flunixin meglumine. According to these results, flunixin meglumine is genotoxic in mice lymphocytes treated in vitro, but has not mutagenic activity in vivo under micronucleus (MN) test conditions.