Tocolytic Effects of Diclofenac Potassium and Diclofenac Sodium on Cattle Myometrium Pre-Incubated with PCB-153

Abstract

In this study, the tocolytic effects of the potassium and sodium salts of diclofenac, a non-steroidal anti-inflammatory drug (NSAID), on cattle myometria were investigated in the presence of an estrogenic polychlorinated biphenyl congener 2,2',4,4',5,5'-hexachlorobiphenyl (PCB-153). The uterine samples were obtained from newly slaughtered, non-pregnant cattle more than two years old and in the anoestrus stage. Eight groups were constituted for testing (each group contained 8 strips from two animals, with 4 from each); there were four control groups (diclofenac potassium 24 h and 48 h; diclofenac sodium 24 h and 48 h) and four groups for PCB-153 (diclofenac potassium 24 h and 48 h; diclofenac sodium 24 h and 48 h). The control groups were incubated in physiological salt solution (PSS) for 24 or 48 hours and the PCB-153 groups were incubated in PSS which contained 100 ng/mL of PCB-153, for either 24 h or 48 h. After the incubation period, the strips were hung and incubated in the tissue bath system until spontaneous contractions occurred. Oxytocin (OT) was administered at 0.5 nM to the strips in all groups for the stimulation of spontaneous contractions. Diclofenac potassium and diclofenac sodium were then administered cumulatively in the range of 1x10(-7) to 7x10(-4) M to the strips of all groups to the maximum inhibitory effect was observed. After each application, isometric uterine contractions were recorded for 20 minutes. Mean peak amplitude (P-MAX), frequency (beats per minutes, BPM) and area under the curve (AUC) values of the myometrial contractions, which are criteria for determining drug effects, were calculated from the curve and evaluated statistically. The inhibitory concentration 50 (IC50) values were calculated for the BPM, P-MAX and AUC values of the myometrial contractions. Finally, the tocolytic effects of diclofenac potassium and diclofenac sodium on the contractions of cattle uterine strips pre-incubated with PCB-153, were determined.