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Caffeine decreases the occurrence of cadmium-induced forelimb ectrodactyly in C57BL/6J mice
1Department of Biological Sciences, DePaul University, Chicago, Illinois 60614, USA.
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.
Insights
Caffeine can reduce birth defects caused by cadmium exposure in mice. This study shows caffeine ameliorates cadmium-induced forelimb ectrodactyly, offering potential insights into preventing teratogenic effects.
Area of Science:
- Developmental toxicology
- Pharmacology
Background:
- Cadmium (Cd) is a known animal teratogen.
- Caffeine is a widely consumed alkaloid.
- Investigating interactions between teratogens and other agents is crucial for understanding teratogenicity and prevention.
Purpose of the Study:
- To investigate the potential of caffeine to ameliorate cadmium-induced teratogenic effects.
- To examine the impact of caffeine co-administration on cadmium-induced malformations in mice.
Main Methods:
- C57BL/6J mice were exposed to varying doses of cadmium sulfate (Cd) on gestation day 9.
- Immediately following Cd injection, mice received either saline or caffeine (CAFF).
- Fetuses were examined on gestation day 18 for gross morphological malformations, specifically ectrodactyly.
Main Results:
- Caffeine significantly reduced the incidence of cadmium-induced forelimb ectrodactyly in both medium and high-dose Cd groups.
- Bilateral ectrodactyly was also decreased with caffeine co-treatment.
- While other Cd-induced abnormalities trended downward with caffeine, the reduction was not statistically significant. Litter size, fetal weight, fetal mortality, and dam weight were unaffected.
Conclusions:
- A subteratogenic dose of caffeine can ameliorate cadmium-induced forelimb ectrodactyly in the Cd-sensitive C57BL/6J mouse strain.
- This finding suggests a potential protective role for caffeine against specific teratogenic effects of cadmium.
