Development and experimental assessment of a terpenoid-based radioprotective formulation: Radioprotective and radiotherapeutic properties

Introduction. The use of nuclear energy may give rise to emergency situations accompanied by the release of radioactive elements into the environment, potentially leading to radiation injuries to personnel of such enterprises or the entire population. In this context, the development of effective and safe approaches for protecting the body from radiation injuries remains highly relevant [1].

Objective. Study of the radioprotective properties of purified turpentine oil (PTO) and its combination with sunflower oil.

Materials and methods. At the first stage of research, the composition of PTO was determined and an optimal solvent was selected. The administration route (subcutaneous, intraperitoneal, intramuscular) of turpentine-oil solutions (at doses of 1806 mg/kg, 1290 mg/kg, 774 mg/kg, 516 mg/kg, and 2580 mg/kg) in 360 mice of both sexes (weighing 18–20 g) was established. At the second stage, the radioprotective efficacy of turpentine–oil solutions was evaluated in 50 white mice (70%, 50%, 30%, 20% turpentine-oil solutions were administered intramuscularly at doses of 1806 mg/kg, 1290 mg/kg, 774 mg/kg, 516 mg/kg 24 h before and after irradiation at a dose of 8.0 Gy (LD_100/30)). At the third stage, the optimal dose ensuring the greatest radioprotective efficacy was determined in 120 white mice of both sexes (irradiation at a dose of 7.7 Gy (LD_100/30); intramuscular administration of a 70% turpentine–oil solution at doses of 1806 mg/kg, 180.6 mg/kg, 90.3 mg/kg, 45.15 mg/kg, 22.57 mg/kg 72 h before and after irradiation). At the fourth stage, the radioprotective efficacy of 50% and 70% turpentine–oil solutions was evaluated in 36 outbred white rats of both sexes (irradiation at a dose of 9.3 Gy; after 3 days, a single subcutaneous administration of PTO at a dose of 258 mg/kg, anti-radiation serum at a dose of 50 mg/kg; intramuscular administration of a 70% turpentine–oil solution at a dose of 90.3 mg/kg, a 50% solution at a dose of 64.5 mg/kg). The content of malondialdehyde in the blood serum was determined on days 3, 5, 7, and 14 after irradiation. At the fifth stage, the optimal timing for the administration of the 70% turpentine–oil solution was determined in 80 white mice irradiated at a dose of 8.0 Gy. Statistical data analysis was performed using the GraphPadPrism v. 8.0 software package.

Results. Highly purified, high-oleic refined sunflower oil was identified as the optimal solvent for PTO. The preferred route of administration is intramuscular for turpentine–oil solutions and subcutaneous for PTO. The most pronounced radioprotective activity was observed for 70% and 50% turpentine–oil solutions administered as a single intramuscular injection 24 h before and after irradiation. To ensure 80% survival of lethally irradiated animals with a single prophylactic use and 60% survival with therapeutic use, intramuscular administration of the developed agent at doses of 90.3–180.6 mg/kg is required during the first 12 days before or during the first 4 days after lethal irradiation. The application of turpentine–oil solutions in various concentrations modified the course of the pathological process: by day 5 after treatment initiation, lethally irradiated animals showed a decrease in lipid peroxidation intensity.

Conclusions. A radioprotective agent has been developed that exerts both prophylactic and therapeutic effects by inhibiting lipid peroxidation products induced by ionizing radiation. The formulation is characterized by a a simple preparation technology, an effective route of administration, and an optimized ratio of components that ensures good absorption. As a result, a single intramuscular injection of the developed formulation can serve as an alternative to prolonged oral administration of terpenoid-based biologically active compounds.

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