Chan Louis Yik-Si, Chiu Pui Yu, Siu Nelson S S, Wang Chi Chiu, Lau Tze Kin
Department of Obstetric and Gynaecology, The Chinese University of Hong Kong, Prince of Wales Hospital, Hong Kong, Shatin, PR China.
Reprod Toxicol. 2002 Nov-Dec;16(6):841-4. doi: 10.1016/s0890-6238(02)00047-3.
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.
双氯芬酸在动物中具有胚胎毒性，但其胚胎毒性机制尚未完全明确。我们推测双氯芬酸诱导的胚胎毒性可能与氧自由基损伤有关。在妊娠9.5天时取出大鼠胚胎，并在含有不同浓度双氯芬酸的培养基中培养。通过测量8-异前列腺素F2α水平来评估双氯芬酸对胚胎氧自由基含量的直接影响。我们发现，暴露于高浓度双氯芬酸（7.5和15.0μg/ml）的胚胎，其8-异前列腺素F2α水平（分别为2.85和3.50 pg/mm胚胎冠臀长）显著高于对照组（1.73 pg/mm，P<0.05），而暴露于低浓度双氯芬酸（1.5μg/ml）的胚胎，其8-异前列腺素F2α水平为2.54 pg/mm，与对照组无显著差异。高浓度组胚胎的形态学评分中位数也低于对照组（39.0对44.0，P<0.05）。这些结果表明，双氯芬酸诱导的胚胎病可能与氧自由基损伤有关。
