Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactylyin C57BL/6J mice

Background: Cadmium is a well-known animal teratogen. Caffeine is an alkalo id widely consumed by humans. Interactions between teratogens and nonterato genic doses of other agents are becoming widely studied, as they may shed l ight on understanding mechanisms of teratogenicity or possible prevention o f teratogenic effects. Methods: 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, immediat ely 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 ectrodac tyly and other gross morphological malformations. Results: Amelioration of cadmium-induced forelimb ectrodactyly by GAFF was seen in both the high-dose cadmium (HDCd = 65.4%, HDCd+CAFF = 39.2%) and me dium-dose cadmium (MDCd = 46.2%, MDCd+GAFF = 20.8%) treatment groups (P < 0 .025). Bilateral expression of ectrodactyly was also decreased in the prese nce of caffeine. A statistically significant reduction in Cd-induced abnorm alities, including: eye, abdominal, and other skeletal defects, was not see n with caffeine addition, although they did trend downward in the caffeine- supplemented groups. Lifter size, fetal weight, fetal mortality, and dam we ight also were not affected by co treatment with caffeine. Conclusions: This study provides evidence that a subteratogenic dose of caf feine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensit ive C57BL/6J inbred mouse strain. (C) 2000 Wiley-Liss, Inc.