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Use of the chick embryo for pharmacological screening of retinoids
M Démarchez1, J Eustache, B Shroot
1Centre International de Recherches Dermatologiques, Sophia Antipolis, Valbonne, France.
Abstract:
Retinoic acid and some selected analogs were tested to evaluate their effect on skin morphogenesis and toxicity in the chick embryo. Retinoids dissolved in dimethyl sulfoxide were injected at doses varying from 10 pmol to 10 mumol into the amniotic cavity of 10-day-old chick embryos (n = 20). At 16 days of incubation, the eggs were opened to record the number of dead embryos and the number of embryos presenting club-shaped feathers. A lethal embryotoxic dose (LED50d16) which, at 16 days of incubation, provokes the death of 50% of the embryos and an effective dose (ED50) which induces production of club-shaped feathers in 50% of surviving embryos were then calculated using log-probit analysis. Retinoids could be classified according to their ED50. For example, arotinoid Ro 13-7410 appears approximately 1,000 times more active than all transretinoic acid. However, the analogs which are more active are also more toxic. The assay described in the present study appears to be a simple and useful model for the screening of retinoids.
Insights
This study evaluated retinoids' effects on chick embryo skin development and toxicity. More potent retinoids showed higher toxicity, indicating a trade-off for potential therapeutic applications.
Area of Science:
- Developmental Biology
- Toxicology
- Pharmacology
Background:
- Retinoic acid and its analogs are crucial signaling molecules in embryonic development.
- Understanding retinoid effects on skin morphogenesis and toxicity is vital for therapeutic development.
- Chick embryo models offer a robust system for evaluating developmental toxicity and efficacy.
Purpose of the Study:
- To assess the impact of retinoic acid and selected analogs on chick embryo skin morphogenesis.
- To determine the toxicity profiles of various retinoids in a developing chick embryo model.
- To establish a simple and effective screening assay for retinoid activity and toxicity.
Main Methods:
- Administration of retinoids dissolved in dimethyl sulfoxide via intra-amniotic injection to 10-day-old chick embryos.
- Incubation until day 16 to assess embryo survival and feather development.
- Calculation of lethal embryotoxic dose (LED50d16) and effective dose (ED50) using log-probit analysis.
Main Results:
- Retinoids exhibited varying degrees of efficacy in inducing club-shaped feathers, with arotinoid Ro 13-7410 being significantly more potent than all-trans retinoic acid.
- A direct correlation was observed between retinoid potency and toxicity, with more active compounds also demonstrating higher lethality.
- The study successfully classified retinoids based on their ED50 values, highlighting differential activity.
Conclusions:
- The chick embryo assay provides a simple, effective, and reproducible model for screening retinoid activity and toxicity.
- Potency and toxicity are closely linked in retinoids, a critical consideration for drug development.
- This model aids in the selection of retinoids with optimal efficacy and acceptable safety profiles for further investigation.