Lutz J, Beck S L
Department of Biological Sciences, DePaul University, Chicago, Illinois 60614, USA.
Teratology. 2000 Nov;62(5):325-31. doi: 10.1002/1096-9926(200011)62:5<325::AID-TERA6>3.0.CO;2-H.
Cadmium is a well-known animal teratogen. Caffeine is an alkaloid widely consumed by humans. Interactions between teratogens and nonteratogenic doses of other agents are becoming widely studied, as they may shed light on understanding mechanisms of teratogenicity or possible prevention of teratogenic effects.
C57BL/6JBK mice were injected intraperitoneally (ip) with cadmium sulfate (Cd) at 0, 1.00 (LDCd), 2.50 (MDCd), or 5.00 (HDCd) mg/kg, immediately followed by subcutaneous (sc) administration of 0 or 50 mg/kg caffeine (CAFF) on gestation day (GD) 9. Fetuses were examined on GD 18 for ectrodactyly and other gross morphological malformations.
Amelioration of cadmium-induced forelimb ectrodactyly by CAFF was seen in both the high-dose cadmium (HDCd = 65.4%, HDCd+CAFF = 39.2%) and medium-dose cadmium (MDCd = 46.2%, MDCd+ CAFF = 20.8%) treatment groups (P < 0.025). Bilateral expression of ectrodactyly was also decreased in the presence of caffeine. A statistically significant reduction in Cd-induced abnormalities, including: eye, abdominal, and other skeletal defects, was not seen with caffeine addition, although they did trend downward in the caffeine-supplemented groups. Litter size, fetal weight, fetal mortality, and dam weight also were not affected by co-treatment with caffeine.
This study provides evidence that a subteratogenic dose of caffeine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensitive C57BL/6J inbred mouse strain.
镉是一种广为人知的动物致畸剂。咖啡因是人类广泛消费的一种生物碱。致畸剂与其他非致畸剂量药物之间的相互作用正得到广泛研究，因为它们可能有助于理解致畸机制或预防致畸效应。
对C57BL/6JBK小鼠在妊娠第9天腹腔注射0、1.00（低剂量镉，LDCd）、2.50（中剂量镉，MDCd）或5.00（高剂量镉，HDCd）mg/kg硫酸镉（Cd），随后立即皮下注射0或50mg/kg咖啡因（CAFF）。在妊娠第18天检查胎儿有无缺指（趾）畸形及其他大体形态畸形。
在高剂量镉（HDCd = 65.4%，HDCd + CAFF = 39.2%）和中剂量镉（MDCd = 46.2%，MDCd + CAFF = 20.8%）治疗组中，均可见咖啡因改善镉诱导的前肢缺指（趾）畸形（P < 0.025）。在有咖啡因存在的情况下，缺指（趾）畸形的双侧表达也有所降低。虽然在添加咖啡因的组中镉诱导的异常（包括眼睛、腹部和其他骨骼缺陷）有下降趋势，但未观察到统计学上的显著降低。同时给予咖啡因对窝仔数、胎儿体重、胎儿死亡率和母鼠体重也没有影响。
本研究提供了证据表明，低于致畸剂量的咖啡因可改善镉敏感的C57BL/6J近交系小鼠中镉诱导的前肢缺指（趾）畸形。
