Using silkworms to establish alternative animal models for evaluation of drug-induced tissue injury

Abstract

Evaluation of tissue injury induced by chemicals is crucial to drug development. Mice and rats, which are effectively used to analyze drug-induced tissue injury, present problems in terms of cost and ethical issues. Although alternative methods have been developed using in vitro techniques or invertebrates, evaluation of ADME and the size of animals are still issues that need to be addressed. Use of silkworms can resolve these problems. Silkworms have pharmacokinetic characteristics similar to those of mammals. Injection of various hepatotoxic chemicals also leads to elevated alanine aminotransferase (ALT) activity in the hemolymph of silkworms. Furthermore, transparent transgenic silkworms expressing GFP have been produced to facilitate continuous analysis without the need to collect hemolymph. Analyses using this silkworm have indicated that the intensity of GFP fluorescence observed on the body surface of the silkworm decreases in a time- and dose-dependent manner when hepatotoxic chemicals are injected. These results suggest that the silkworms can serve as alternative animal model for evaluation of drug-induced tissue injury.