Generative Function of Female Rats Upon Intragastric Administration of Tablets of the New Steroid Drug Gestobutanoil
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Pharmaceutical Chemistry Journal, Vol. 54, No. 5, August, 2020 (Russian Original Vol. 54, No. 5, May, 2020)
GENERATIVE FUNCTION OF FEMALE RATS UPON INTRAGASTRIC ADMINISTRATION OF TABLETS OF THE NEW STEROID DRUG GESTOBUTANOIL N. I. Sheina,1,* V. A. Parshin,1 V. V. Kolesnikova,1 L. I. Myalina,1 L. P. Sazonova,1 T. A. Fedotcheva,1 and N. L. Shimanovskii1 Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 54, No. 5, pp. 11 – 15, May, 2020.
Original article submitted February 17, 2020. The generative function of female rats upon intragastric administration of tablets of gestobutanoil at doses of 0.25 and 2.5 mg/kg (calculated doses corresponding to the therapeutic dose and ten times higher) was studied. Gestobutanoil was administered two weeks before pregnancy, which corresponded to 2 – 3 estrous cycles. Gestobutanoil at a dose of 0.25 mg/kg exhibited progestogen activity. The duration of estrus, the fertility index, and the numbers of pregnancy corpus lutea and live fetuses increased in female rats. Administration of gestobutanoil at a dose of 2.5 mg/kg produced a contraceptive effect that manifested as a prolonged estrous cycle and a reduction of fertility and numbers of corpus lutea and fetuses. Gestobutanoil at both doses did not produce a teratogenic effect and did not affect the vitality of F1 offspring (survival, body-weight dynamics, sensory-motor behavior development). Keywords: progestogen, steroid, gestobutanoil, generative function, estrous cycle, pregnancy, offspring.
Fertility and miscarriage problems are becoming more significant for medical science and practice because of the worsening reproductive health and demographic situation in both Russia and most developed countries of Europe and America. The incidence of infertile couples is high and reaches 25 – 30% of all conjugal pairs according to the WHO [1]. The discovery and development of new effective methods for diagnosis, treatment, and prevention of female reproductive diseases are necessary because their number is constantly growing in most developed countries. Also, WHO experts consider that issues of family planning and control of reproductive functions to guarantee the birth of only preferred children are also critical in all countries [2, 3]. Synthetic gestagens, i.e., progesterone analogs, are widely used in obstetric-gynecological practice to treat the luteal phase of the menstrual cycle; to treat and prevent hyperplastic endometrial processes, endometriosis, and endocrine forms of infertility; and to remove the threat of mis1 *
carriage. They are also used as replacement hormonal therapy in women with physiological or pathological amenorrhea. Several progestogens are cytotoxic to female reproductive tumors [4, 5]. Progestogens are classified as combined peroral contraceptives. Purely progestogen contraception is widely employed [6, 7]. Previous research showed that the butyl ester 17a-acetoxy-3b-hydroxy-6-methylpregna-4,6-dien-20-one (gestobutanoil) displayed high long-term gestagenic activity and bioavailability [8, 9]. The compoun
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