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Subchronic Toxicity Study of Oral Anthrafuran on Rabbits
Michael I Treshchalin1, Helen M Treshalina1, Vasilisa A Golibrodo1
1Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia.
Abstract:
A new antitumor multi-target drug anthrafuran, with cellular targets such as topoisomerase I/II and some protein kinases, was obtained in Gause Institute of New Antibiotics and was demonstrated to have a reliable specific effect on different murine and human tumor models by oral administration. In this study, we focused on the evaluation of subchronic toxicity of oral anthrafuran drug formulation (AF) on Chinchilla rabbits. The absence of any changes in the condition or behavior of animals was shown for oral anthrafuran. Changes with reversible and dose-dependent hepato- and nephrotoxicity at low doses, as well as hemato- and gastrointestinal toxicity at high doses, were confirmed pathomorphologically. The identified toxic properties are extremely valuable, since oral anthrafuran does not have the limiting cardio- and myelotoxicity. Anthrafuran with 2 mg/kg/day or 6 mg/kg/day doses was administrated orally over 15 days. Investigations include assessment of the body weight, hematological and serum biochemical parameters and urinalysis, electrocardiography and pathomorphological evaluation of the internal organs. Quantitative data were processed statistically with Student's t-Test, p < 0.05. Revealed during the subchronic study were the favorable toxicological properties of oral anthrafuran as opposed to clinical anthracyclines, oral idarubicin, or parenteral doxorubicin, which allows it to be considered promising for further research.
Insights
New antitumor drug anthrafuran (AF) shows promising oral administration in toxicity studies. While reversible hepato- and nephrotoxicity occurred at low doses, and hemato- and gastrointestinal toxicity at high doses, it lacks cardio- and myelotoxicity, unlike current treatments.
Area of Science:
- Pharmacology
- Toxicology
- Oncology
Background:
- Anthrafuran (AF) is a novel multi-target antitumor agent effective against various tumor models via oral administration.
- AF targets topoisomerase I/II and protein kinases, offering a new therapeutic avenue in cancer treatment.
Purpose of the Study:
- To evaluate the subchronic toxicity of orally administered anthrafuran (AF) drug formulation in Chinchilla rabbits.
- To compare the toxicological profile of oral AF with existing clinical anthracyclines.
Main Methods:
- Subchronic oral administration of AF at 2 mg/kg/day and 6 mg/kg/day for 15 days.
- Comprehensive assessments including body weight, hematology, serum biochemistry, urinalysis, electrocardiography, and pathomorphological evaluation.
- Statistical analysis using Student's t-Test (p < 0.05).
Main Results:
- No significant changes in animal condition or behavior observed.
- Reversible, dose-dependent hepato- and nephrotoxicity at low doses.
- Hematological and gastrointestinal toxicity observed at high doses.
- Crucially, absence of limiting cardiotoxicity and myelotoxicity.
Conclusions:
- Oral anthrafuran (AF) exhibits a favorable toxicological profile compared to clinical anthracyclines like oral idarubicin or parenteral doxorubicin.
- The identified toxicities are manageable and reversible, suggesting AF's potential as a promising oral antitumor drug.
- Further research into anthrafuran (AF) is warranted due to its unique therapeutic and safety advantages.

