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Open Access Research article

Evaluation of drug-induced tissue injury by measuring alanine aminotransferase (ALT) activity in silkworm hemolymph

Yoshinori Inagaki1, Yasuhiko Matsumoto1, Keiko Kataoka2, Naoya Matsuhashi2 and Kazuhisa Sekimizu12*

Author Affiliations

1 Laboratory of Microbiology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

2 Genome Pharmaceuticals Institute Co., Ltd., The University of Tokyo Entrepreneur Plaza, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

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BMC Pharmacology and Toxicology 2012, 13:13  doi:10.1186/2050-6511-13-13

Published: 8 November 2012

Abstract

Background

Our previous studies suggest silkworms can be used as model animals instead of mammals in pharmacologic studies to develop novel therapeutic medicines. We examined the usefulness of the silkworm larvae Bombyx mori as an animal model for evaluating tissue injury induced by various cytotoxic drugs. Drugs that induce hepatotoxic effects in mammals were injected into the silkworm hemocoel, and alanine aminotransferase (ALT) activity was measured in the hemolymph 1 day later.

Results

Injection of CCl4 into the hemocoel led to an increase in ALT activity. The increase in ALT activity was attenuated by pretreatment with N-acetyl-L-cysteine. Injection of benzoic acid derivatives, ferric sulfate, sodium valproate, tetracycline, amiodarone hydrochloride, methyldopa, ketoconazole, pemoline (Betanamin), N-nitroso-fenfluramine, and D-galactosamine also increased ALT activity.

Conclusions

These findings indicate that silkworms are useful for evaluating the effects of chemicals that induce tissue injury in mammals.

Keywords:
Silkworm; Alanine aminotransferase; Tissue injury; Animal model