Diclofenac-induced embryotoxicity is associated with increased embryonic 8-isoprostaglandin F2alpha level in rat whole embryo culture.
Diclofenac is embryotoxic in animals but the mechanism of its embryotoxicity is not fully understood. We postulated that diclofenac-induced embryotoxicity might be related to free oxygen radical damage. Rat embryos were explanted at 9.5 days gestation and cultured in medium containing various concentrations of diclofenac. The direct effect of diclofenac on embryonic free oxygen radical content was evaluated by measuring the 8-isoprostaglandin F2alpha level. We found that embryos exposed to high concentrations of diclofenac (7.5 and 15.0 micro g/ml) had significantly higher levels of 8-isoprostaglandin F2alpha (2.85 and 3.50 pg/mm embryonic crown-rump length, respectively) than the control group (1.73 pg/mm, P<0.05), while the 8-isoprostaglandin F2alpha level in embryos exposed to low concentration of diclofenac (1.5 micro g/ml) was 2.54 pg/mm, which was not significantly different from the control group. Median embryo morphologic score was also lower in the high concentration group compared to the control group (39.0 versus 44.0, P<0.05). These results suggest that diclofenac-induced embryopathy may be related to free oxygen radical damage.
Chan
Louis Yik-Si
LY
Department of Obstetric and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Shatin, PR China. lyschan@cuhk.edu.hk
Chiu
Pui Yu
PY
Siu
Nelson S S
NS
Wang
Chi Chiu
CC
Lau
Tze Kin
TK
D000014:Abnormalities, Drug-Induced; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D018568:Crown-Rump Length; D004008:Diclofenac / Q000633:toxicity*; D015237:Dinoprost / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian / Q000187:drug effects* / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D028441:F2-Isoprostanes / Q000378:metabolism*; D015227:Lipid Peroxidation / Q000187:drug effects; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
D000894:Anti-Inflammatory Agents, Non-Steroidal; D028441:F2-Isoprostanes; D004008:Diclofenac; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost