Modification of Radiation Effects Preclinical Studies of the Preventive Agent for Complications of Radiotherapy T1082. Assessment of Toxic and Radioprotective Effects during Enteral Administration

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Preclinical studies conducted a toxicological and radiobiological study of a drug for enteral prophylaxis of radiation therapy complications based on the NOS inhibitor T1082. It was established that T1082 is safe when administered intragastrically: the LD10/14 and LD50/14 values for mice and rats are similar, amounting to 2040–2090 mg/kgand 2600–2650 mg/kg (class 5 according to GOST 32419–2022 – low toxicity). Comparison of these parameters with previously obtained estimates of radioprotective doses of T1082 for mice with intragastric administration (ED50 – 88 mg/kg; range of optimal radioprotective dosesED 84–98 – 140–220 mg/kg) indicates the safety of the enteral route of T1082 administration: the therapeutic index LD50/ED50 is 30, and the values of optimal radioprotective doses are an order of magnitude lower than the maximum tolerated ones (1/15–1/10 LD10). Studies of local irritant effect have shown that only in high concentrations (10%) T1082 can cause a weak and transient reaction of the gastrointestinal mucosa, while with multiple intragastric administration in optimal radioprotective doses and moderate concentrations (1–2%) there is no irritating effect. In a skin radiation reaction model in piglets, T1082 at a dose of 23.3 mg/kgdemonstrated high efficacy, statistically significantly limiting the severity of skin lesions and reducing the incidence of key pathological changes in irradiated skin. This confirms the adequacy of the model used for interspecies dose transfer. The obtained data demonstrate the potential safety of the developed agent and the feasibility of developing a finished dosage form based on T1082 for enteral administration.

Sobre autores

M. Filimonova

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: vladimirovna.fil@gmail.com
Obninsk, Russia

V. Rybachuk

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: rybachukvitaliy@gmail.com
ORCID ID: 0000-0002-1178-3560
Obninsk, Russia

A. Kosachenko

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: filatovadaria.nik@gmail.com
ORCID ID: 0000-0003-2173-388X
Obninsk, Russia

K. Nikolaev

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Obninsk, Russia

A. Gorbachev

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: axel.gorbach@gmail.com
ORCID ID: 0009-0008-6475-9004
Obninsk, Russia

D. Filatova

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: filatovadaria.nik@gmail.com
ORCID ID: 0009-0005-3866-2792
Obninsk, Russia

O. Soldatova

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: oliasoldatt@yandex.ru
ORCID ID: 0000-0002-1178-3560
Obninsk, Russia

A. Shitova

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: annaredrose@mail.ru
ORCID ID: 0000-0001-5512-9096
Obninsk, Russia

G. Demyashkin

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: axel.gorbach@gmail.com
ORCID ID: 0000-0001-8447-2600
Obninsk, Russia

E. Litun

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: evlitun@mail.ru
Obninsk, Russia

V. Saburov

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Obninsk, Russia

S. Koryakin

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Obninsk, Russia

A. Pankratov

National Medical Research Center of Radiology, Ministry of Health of the Russian Federation

Email: andreymnoi@mail.ru
ORCID ID: 0000-0001-7291-9743
Obninsk, Russia

S. Ivanov

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Email: ivanov.obninsk@mail.ru
ORCID ID: 0000-0001-7689-6032
Obninsk, Russia

P. Shegai

National Medical Research Center of Radiology, Ministry of Health of the Russian Federation

Email: andreymnoi@mail.ru
Obninsk, Russia

A. Kaprin

National Medical Research Center of Radiology, Ministry of Health of the Russian Federation

Email: kaprin@mail.ru
ORCID ID: 0000-0001-8784-8415
Obninsk, Russia

A. Filimonov

A. Tsyb Medical Radiological Research Centre — the branch of the National Medical Research Radiological Centre of the Ministry of Health of the Russian Federation

Obninsk, Russia

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