Evaluation of neurotoxicity of anthrafuran, a new antitumor drug from the anthracenediones class

Background. Neurotoxicity is a side effect of anthracycline antibiotics that has been identified during clinical use. while this type of toxicity may not be limiting, it can significantly affect the quality of life for patients. In the Gause Institute of New Antibiotics an antitumor compound called anthrafuran has developed, that is similar in structure to anthracyclines. This compound has shown high activity in experiments using mouse models of transplanted tumors when administered orally. Anthrafuran has the ability to penetrate the blood-brain barrier, so a study of its neurotoxicity was previously conducted at the maximum tolerated dose.

Aim. To experimentally evaluate the neurotoxicity of anthrafuran when it is administered orally at both a therapeutic dose and three times the therapeutic dose.

Materials and methods. Female Albino rats were used in the experiment. The animals were kept under conditions accordance to GOST 33044–2014 “Principles of good laboratory practice”. Anthrafuran substance was administered orally as a 1,2 % solution in 5 % glucose for injection at doses of 20 and 60 mg/kg once. Motor and research activity of the animals was evaluated in an Open Field test setting 4 hours, one day, and one month after administration. To detect cognitive dysfunction, rats were trained in a T-maze with food reward 3–5 days after drug administration.

Results. Administration of the drug at a therapeutic dose of 20 mg/kg did not cause any abnormal behavior in animals in the Open Field or affect the ability to learn in the T-maze. However, at a dose three times higher than the therapeutic dose (60 mg/kg), anthrafuran decreased the research activity of rats in the Open Field 4 and 24 hours after administration and inhibited the ability to acquire learning in T-maze.

Conclusion. The use of anthrafuran in a therapeutic dose did not cause pronounced neurotoxic reactions. In order to further promote the drug, it is necessary to conduct an in-depth study on the effect of the substance and dosage forms on the behavioral responses and cognitive abilities of rats.

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