Investigation of flurbiprofen genotoxicity and cytotoxicity in rat bone marrow cells

Abstract

This study was performed to investigate cytogenetic effects of NSAID flurbiprofen which was used as active ingredient in some analgesic, antipyretic and anti-inflammatory drugs. Genotoxic effect of flurbiprofen was investigated using in vivo chromosome aberration (CA) test and random amplified polymorphic DNA-polymerase chain reaction (RAPD-PCR) test. Also, oxidative stress potential of flurbiprofen was determined by measuring total oxidant and antioxidant level which occurred with flurbiprofen treatment in rat peripheral blood. For these purposes, rats were treated with three concentrations of flurbiprofen (29.25, 58.50 and 117 mg/kg, body weight) in single dose at two different treatment periods (12 and 24 h). According to the results, flurbiprofen did not affect chromosome aberrations in rat bone marrow cells with CA test. In RAPD-PCR test, polymorphic bands were unaffected. Also, test substance did not change total oxidant and antioxidant status (except for 58.50 and 117 mg/kg, 12 h) and therefore it did not lead to significant increase on oxidative stress (again except 58.50 and 117 mg/kg, 12 h). However, flurbiprofen reduced to mitotic indexes and these reductions were dose-dependent for 12 h treatment. In summary, flurbiprofen did not show significant genotoxic effect. But it caused cytotoxicity in rat bone marrow cells.

In vitrocytogenetic evaluation of the particular combination of flurbiprofen and roxithromycin

“…This is the first report mentioned about DNA protective effect of a NSAID. This results supports the findings about FLB's genotoxicity (Timocin & Ila, 2015;Timocin et al, 2016). This first report of RXM's DNA damaging and protection activity showed that RXM did not have damaging or protection activity on DNA.…”

“…In our previous study, FLB reduced mitotic index (cytotoxicity marker) (Carrano & Natarajan, 1988) for 12 and 24 h treatment periods in rat bone marrow cells. Also, this reduction was concentration dependent for 12 h (Timocin & Ila, 2015). In an another study, 200 mM FLB (48 h) lead to apoptosis in squamous cell carcinoma lines in vitro, inducing caspase-3 enzyme activity (Bock et al, 2007).…”

“…In a previous study, FLB alone did not induce chromosome aberration and polymorphic bands (RAPD-PCR) in rat bone marrow cells (Timocin & Ila, 2015). There is not any study about the genotoxic potential of RXM.…”

“…In our previous study, FLB did not change total oxidant and antioxidant status and hence oxidative stress in rat bone marrow cells (Timocin & Ila, 2015). According to researchers, FLB did not have any effect on oxidative stress induced (3) 20 mg/mL flurbiprofen + 50 mg/mL roxithromycin; (4) 30 mg/mL flurbiprofen + 100 mg/mL roxithromycin; (5) 40 mg/mL flurbiprofen + 200 mg/mL roxithromycin; (6) 2 mL DMSO + 3 mL H 2 O 2 ; (7) 20 mg/mL flurbiprofen + 50 mg/mL roxithromycin + 3 mL H2O2; (8) 30 mg/mL flurbiprofen + 100 mg/mL roxithromycin + 3 mL H2O2; (9) 40 mg/mL flurbiprofen + 200 mg/mL roxithromycin + 3 mL H 2 O 2 .…”

“…In one study, FLB did not have any genotoxic effect on peripheral blood cells of human who used FLB for two weeks (Kullich & Klein, 1986). There are some reports regarding cytotoxic and anti-proliferative effects of FLB (Kusuhara et al, 1999;Jurima-Romet et al, 1994;Masubuchi et al, 1998;Zielinska-Przyjemska et al, 2008) similarly our previous research showed that FLB had cytotoxic effect on cells and negative effect on mitotic index, nuclear division index, and proliferation index in vitro while it did not induce chromosome aberration, micronuclei formation, and sister chromatid exchange (Timocin & Ila, 2015;Timocin et al, 2016). We did not find any reports about the genotoxic potential of RXM, although in our unpublished study, RXM did not show any genotoxic effect in human lymphocytes in chromosome aberration, sister chromatid exchange, and micronucleus tests.…”