Relevance. In the experiment, it was shown that in rats with a sulpiride induced prostate hyperplasia (SGP) which was treated by the Maclura Pomifera oil extract (OEM), a prostatic index is normalized, biochemical indicators and morphofunctional state of the prostate are improved. However, the mechanism of implementing corrective influence remains unknown.
Objective: to exam the contribution of hormonally mediated signaling pathways of the mechanism of pharmacological effect of oil extract in the form of rectal suppositories at the experimental hyperplasia of the prostate in rats.
Materials and methods. On 60 rats of both sexes, acute toxicity of the active substance was studied with intragastric administration of OEM (dose on the active substance 5000 mg/kg, n = 12) or suppositories mass with OEM (dose for the active substance of 1500 mg/kg, n = 12). Under rectal administration, toxicity was investigated with the introduction of OEM (dose of the active substance 1000 mg/kg, n = 12) or suppositories mass with OEM (dose for the active substance 300 mg/kg, n = 12). A group of intact control amounted to 12 rats. The SGP model was created in rats (age 9-11 months, body mass 330-360 g, n = 18) by sulpiride (40 mg / kg, i.p., 30 days). The rats of the control group (n = 6) were obtained with 0.5 ml of 0.9% NaCl, i.m. From 31 to 51 days of the experiment, rats in the therapeutic mode were treated with OEM suppositories (380 mg/kg, n = 12) or a reference drag Prostaplant Forte (35 mg/kg, n = 6) once a day. The testosterone (Tc) and E2 content, level 5α-dihydrotestosterone (5α-DHT) were determined by the immunoferment method in serum. In the prostate homogenate, the content of 5α-reductase (5αR) was studied, as well as the concentration of androgenic (AR) and estrogenic (Erα) receptors.
Results. Toxic influence on the internal organs and deaths of animals after the introduction of the maximum possible amounts of OEM was not observed. The use of suppositories with OEM in rats with SGP normalized the content of sex hormones. Significant inhibition of 5αR activity and a decrease in the content of AR, as well as an increase in the content of ERα, were detected. The group with the introduction of the Prostaplant forte was observed similar improvements. It was assumed that the implementation of the antiproliferative effect of the MEM is carried out due to the coexpression of the ERα and ERβ, which leads to the blocking of the ERα ability to react to the ligand (estrogen) and to a decrease in cell proliferation.
Conclusions. 1. Extract of Maclura refers to the ІV class of toxicity with intragastric and rectal administration (low-toxic substances). 2. The use of suppositories with OEM in rats with SGPH normalizes the functional activity of the prostate, which is confirmed by the normalization of the content of sex hormones. 3. Extract of Maclura in the prostate cells inhibits 5α-reductase activity, reduces androgen receptors and the testosterone ratio/androgen receptors as the same to drugs with 5α-reductase inhibition action. 4. Phytosuppositories with OEM in a dose of 380 mg/kg do not inferior on the efficiency of the prostatoprotective action of the referens drag Prostaplant forte in a dose of 35 mg/kg.
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