The LD50 Values of Cardiovascular Drugs at Different Developmental Stages in Chick Embryos

Hiroyuki Miyazaki, Takashi Sugiyama and Hideyo Shimada
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University,9-1,Shirokane 5-chome,Minato-ku,Tokyo 108-8641 Japan

Correspondence: Takashi Sugiyama, Ph.D.
Division of Pathophysiology, Center for Clinical Pharmacy and Clinical Sciences, School of Pharmaceutical Sciences, Kitasato University
9-1, Shirokane 5-chome, Minato-ku, Tokyo 108-8641 Japan
Tel / Fax: 03-3446-9036
e-mail: sugiyama@platinum.pharm.kitasato-u.ac.jp

Running Title: LD50 Values of Cardiovascular Drugs in Chick Embryos

Original paper :AATEX 6(1):52-57,1999
Abstract
The LD50 values were determined for cardiovascular drugs in chick embryos at different developmental stages in order to obtain a more precise injection stage for fertile eggs of White Leghorn chickens for the prediction in rodents. First, time-course changes in the weight of fertile eggs, their air sac volume, and weight of each egg component were measured after the initiation of incubation. The weight of whole eggs decreased with incubation, while air sac volume increased. The chick embryos weight increased with decreases in albumen weight. These findings suggest that decreases in whole egg weight are due to decreases in water in the eggs. When the maximum volume of physiological saline or CMC-Na solution was injected into the air sac on different days of incubation the bulk of the vehicle did not prove to be toxic to the chick embryos. Next, several cardiovascular drugs, i.e., aloprenolol, piretanide, dipyridamol, lidocaine, propranolol, canrenoate, disopyramide and reserpine were injected into the air sac of eggs on day 2, 5, 8, or 15 of incubation. Then, the chick embryos were sacrificed on day 20 of incubation, and LD50 values were calculated. The LD50 values of these drugs increased with the developmental stages in chick embryos. The LD50 values in chick embryos on day 2 and 5 of incubation showed a fairly strong correlation to those in mice obtained from the intravenous route. Furthermore, findings obtained on day 2 of incubation were most sensitive and reliable in predicting LD50 values in rodents. In conclusion, when cardiovascular drugs were injected into the air sac of fertile eggs in the early stage of development, i.e., day 2 of incubation, LD50 values in chick embryos could be used to predict the LD50 values in rodents.

Keywords: ; cardiovascular drugs, chick embryo, developmental stage, lethal toxicity


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