Research of acute toxicity of the MM-D37K peptide compound in mice and rats

Автор: Kulinich T.M., Bolchakova O.B., Dzhikiya E.L., Shishkin A.M., Ivanov A.V., Bozhenko V.K.

Журнал: Вестник Российского научного центра рентгенорадиологии Минздрава России @vestnik-rncrr

Рубрика: Молекулярная медицина

Статья в выпуске: 4 т.21, 2021 года.

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Acute toxicity studies are a necessary stage of preclinical studies of drugs. The purpose of this work is to study acute toxicity and to determine the maximum tolerant dose of the peptide drug MM- D37K, with different methods of administration in male and female mice of the CD-1 line and rats SD.Methods. MM-D37K was administered once; intraperitoneal, intravenous, subcutaneous and oral ( per os ) administration were investigated. Doses for oral administration ranged from 5 to 1500 mg / kg, with intraperitoneal, intravenous and subcutaneous methods of administration, doses ranged in mice from 5 to 350 mg/kg, in rats from 5 to 500 mg/kg. Control animals were injected with 1 ml of 1% starch solution. The clinical picture, signs of intoxication and death of animals were evaluated.Euthanasia and pathoanatomic autopsy were performed 14 days after the administration of the peptide drug.Results. The peptide preparation MM-D37K in mature mice and rats of both sexes did not affect the consumption of water and feed, as well as the hematological and biochemical parameters of blood. This phenomenon was shown for different methods of administration and single use. There were no differences between females and males and in the effect of the studied drug. A local irritant effect has been registered with intraperitoneal and subcutaneous administration. The study made it possible to establish the toxic concentrations of MM-D37K, which are significantly higher than the effective therapeutic doses of the drug being developed. This allows planning of further studies and access to clinical trials of the proposed new antitumor drug.

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Acute toxicity, drug safety, cyclin dependent kinase inhibitors, internalized peptides (cell penetrating peptides, cpp)

Короткий адрес: https://sciup.org/149139202

IDR: 149139202

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