Abstract
BackgroundOur 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.ResultsInjection 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.ConclusionsThese findings indicate that silkworms are useful for evaluating the effects of chemicals that induce tissue injury in mammals.
Highlights
Our previous studies suggest silkworms can be used as model animals instead of mammals in pharmacologic studies to develop novel therapeutic medicines
Chemicals Various cytotoxic drugs were purchased, as follows: carbon tetrachloride (CCl4), salicylic acid, ferric sulfate, sodium valproate, N-nitroso-fenfluramine, and D-galactosamine were purchased from Wako Pure Chemical Industries, Osaka, Japan; acetaminophen was purchased from Tocris Biosciences, Ellisville, MO; acetylsalicylic acid was purchased from Cayman Chemical Co., Ann Arbor, MI; tetracycline was purchased from LKT Laboratories Inc., St Paul, MN; amiodarone hydrochloride was purchased from MP Biomedicals, Solon, OH; methyldopa was purchased from Sawai Pharmaceutical Co., Ltd., Osaka, Japan; ketoconazole was purchased from LKT Laboratories Inc.; and pemoline was purchased from Sanwa Kagaku Kenkyusho Co., Ltd., Nagoya, Japan
Elevation of Alanine aminotransferase (ALT) activity in the hemolymph of silkworms injected with carbon tetrachloride (CCl4) CCl4 is generally used as a model compound to evaluate hepatotoxic effects in mammals
Summary
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. Tissue injury induced by chemicals in mammals, including humans, is associated with the rapid development of severe impairment of the organs involved in detoxification, e.g., fulminant hepatic failure [1]. Assessment of chemical-induced tissue injury is crucial in drug discovery. In the development of novel therapeutic medicines, in vivo trials using animal models are essential for predicting toxicity and drug disposition in the human body. The use of mammals for experimental models, is associated with a number of problems, such as high cost and ethical issues. An alternative animal model is needed to overcome these problems
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