Protective effect by melatonin in an experiment with transplantable melanoma B16

Recent studies have shown that the pineal gland hormone melatonin has a variety of regulatory effects of an adaptogen with multimodal capabilities. Currently, the properties of melatonin as an anticarcino-genic agent are being actively studied. Preclinical studies have demonstrated that melatonin in combination with chemotherapeutic agents is capable of producing a synergistic effect in combination therapy for the treatment of melanoma.

The aim of our study was to investigate the effects made by exogenously administered melatonin as monotherapy for the treatment of B16/F10 melanoma transplanted into mature male BDF1 F1 hybrid mice.

Materials and methods. The study was conducted on male BDF1 hybrid mice (F1 generation of C57BL/6 and DBA/2 strains) aged 9 months with a body weight of 23-25 g (n=40) delivered by the lab animal breeding facility at the Ufa Research Institution “Lab animal breeding facility and Vivarium at the Institute of Problems Chemical Physics at the Russian Academy of Sciences”. There were two groups of animals formed, which received B16/F10 melanoma transplanted by standard subcutaneous injection of 0.5 ml of tumor cell suspension in medium 199 (dilution 1:10) in the left side region of the back. One of the groups received intragastrically “Melatonin” (Sigma, USA) at a dose of 5 mg/kg of body weight (Mel group) starting from the 1st day of the tumor transplantation. Animals of the other group received the same volume of medium 199 (comparison group). Mice were provided with free access to water and food for 14 days under natural light. On the 15th day, the animals were withdrawn from the experiment with decapitation under anesthesia. The tumor, lungs, and liver were excised. The tumor mass was determined by the formula as follows: V = π / 6 ∙ D1 ∙ D2 ∙ D3, where D1 is the length; D2 is the width; D3 is the tumor height in cm. The tumor was fixed in 10% neutral formalin and processed in standard manner in alcohols and xylene, followed by pouring into the Histomyx medium (BioVitrum, Russia). Histological sections 5-6 μm thick were prepared, stained with hematoxylin and eosin. Microscopic examination and photography of the obtained preparations were performed with the Leica Microsystem DM 2500 microscope. Using the ImageJ software (Fiji), the nuclear-cytoplasmic ratio of tumor cells (NCR) was calculated. The presence of metastases in the lungs and the liver was macroscopically assessed. The obtained data were statistically processed.

Results. In the Mel group, there was no mortality of mice recorded during the 2 weeks of the experiment. We observed a decrease in the occurrence rate of metastasis, signs of tumor regression in the form of foci of dystrophic and alterative alterations, as well as a decrease in the tumor size. At the same time, death of 4 animals was reported in the comparison group.

Conclusion. It was found that the use of melatonin at a dose of 5 mg / kg of body weight induced a decrease in animal mortality, the occurrence rate of tumor metastasis, as well as a decrease in the tumor size due to dystrophic and alterative processes.

24 | Cardiometry | Issue 33. November 2024