Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice.
BACKGROUND
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.


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, 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.


RESULTS
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.


CONCLUSIONS
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.
Lutz
J
J
Department of Biological Sciences, DePaul University, Chicago, Illinois 60614, USA.
Beck
S L
SL
D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D002104:Cadmium / Q000633:toxicity*; D002110:Caffeine / Q000627:therapeutic use*; D000697:Central Nervous System Stimulants / Q000627:therapeutic use*; D003433:Crosses, Genetic; D004622:Embryo, Mammalian / Q000187:drug effects / Q000473:pathology; D005260:Female; D005333:Fetus / Q000502:physiology; D005552:Forelimb / Q000002:abnormalities* / Q000187:drug effects; D007839:Functional Laterality / Q000187:drug effects; D007279:Injections, Subcutaneous; D008098:Litter Size / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy
D000697:Central Nervous System Stimulants; D002104:Cadmium; D002110:Caffeine