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.

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.