Abstract
Purpose::
To investigate the effect of two fluoroquinolones (pradofloxacin and enrofloxacin) on the cat retina using electroretinogram.
Methods::
Ganzfeld ERGs were recorded under dark and light adapted conditions in 40 cats in 4 groups: CTRL (n = 9): vehicle; PRADO30 (n =10): pradofloxacin 30 mg/kg/day; PRADO50 (n =14): pradofloxacin 50 mg/kg/day, and ENRO (n = 7): enrofloxacin 30 mg/kg/day. Cats were treated orally for 23 days, ERG was performed before treatment and once weekly during treatment period. An extended ISCEV protocol was carried out: 8 steps of increasing luminance (covering 6 log cd.s/m²) to assess: VMax (dark adapted saturated amplitude) and k (luminance inducing VMax/2, as a measure of sensitivity), parameters of the Naka-Rushton function.
Results::
In the CTRL group VMax at base line was 356.73 ±14.82 µV and 335.48 ± 25.59 µV after treatment (p=0.82, average of 4 weeks in treatment); k was -2.49 ± 0.04 log cd.s/m² at baseline and -2.51 ± 0.03 log cd.s/m² after treatment (p=0.30). ENRO administration led to undetectable (semi-saturated) rod b-wave, VMax was reduced to 10.5% of the baseline (414.27 ± 49.17 µV vs. 43.40 ± 10.4 µV after treatment), accompanied by an increase of k by 1 log cd.s/m² (-2.42 ± 0.07 log cd.s/m² at baseline and -1.36 ± 0.085 log cd.s/m² after treatment). Oscillatory potentials (area under the curve), cone b-wave amplitude and 30 Hz flicker amplitude were also reduced: 8.3%, 58.9% and 37.4% of the baseline, resp. (p<0.05). Effects were seen already one week after treatment start, remaining stable. Neither PRADO30 nor PRADO50 showed effects in respect to VMax (362.39 ± 24.44 µV at baseline and 348.06 ± 23.51 µV after treatment; p=0.380; PRADO50) or k (-2.48 ± 0.05 log cd.s/m² at baseline and -2.58 ± 0.042 cd.s/m² after treatment; p=0.120). Oscillatory potentials, cone single flash ERG and flicker were also unaltered (p>0.05).
Conclusions::
Pradofloxacin in doses of 30 and 50 mg/kg/day (6 and 10 times recommended doses) was shown to have no toxic effect whatsoever on rod and cone function in ERG, while cats treated with enrofloxacin 30 mg/kg/day (6 times the recommended dose) presented abnormal ERGs. These results demonstrate that antibiotics with similar molecular structures (pyrrolidine-piperidine replacing the ethyl-piperazine at C- position 7 in enrofloxacin) can present with extremely different retinal toxicity; future toxicological investigations are necessary to define relations between the fluoroquinolone structure and retinal toxicity.
Keywords: electroretinography: non-clinical • retina • antibiotics/antifungals/antiparasitics